stem cell essay

• Open access
• Published: 26 February 2019

Stem cells: past, present, and future

• Wojciech Zakrzewski 1 ,
• Maciej Dobrzyński 2 ,
• Maria Szymonowicz 1 &
• Zbigniew Rybak 1  

Stem Cell Research & Therapy volume  10 , Article number:  68 ( 2019 ) Cite this article

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In recent years, stem cell therapy has become a very promising and advanced scientific research topic. The development of treatment methods has evoked great expectations. This paper is a review focused on the discovery of different stem cells and the potential therapies based on these cells. The genesis of stem cells is followed by laboratory steps of controlled stem cell culturing and derivation. Quality control and teratoma formation assays are important procedures in assessing the properties of the stem cells tested. Derivation methods and the utilization of culturing media are crucial to set proper environmental conditions for controlled differentiation. Among many types of stem tissue applications, the use of graphene scaffolds and the potential of extracellular vesicle-based therapies require attention due to their versatility. The review is summarized by challenges that stem cell therapy must overcome to be accepted worldwide. A wide variety of possibilities makes this cutting edge therapy a turning point in modern medicine, providing hope for untreatable diseases.

Stem cell classification

Stem cells are unspecialized cells of the human body. They are able to differentiate into any cell of an organism and have the ability of self-renewal. Stem cells exist both in embryos and adult cells. There are several steps of specialization. Developmental potency is reduced with each step, which means that a unipotent stem cell is not able to differentiate into as many types of cells as a pluripotent one. This chapter will focus on stem cell classification to make it easier for the reader to comprehend the following chapters.

Totipotent stem cells are able to divide and differentiate into cells of the whole organism. Totipotency has the highest differentiation potential and allows cells to form both embryo and extra-embryonic structures. One example of a totipotent cell is a zygote, which is formed after a sperm fertilizes an egg. These cells can later develop either into any of the three germ layers or form a placenta. After approximately 4 days, the blastocyst’s inner cell mass becomes pluripotent. This structure is the source of pluripotent cells.

Pluripotent stem cells (PSCs) form cells of all germ layers but not extraembryonic structures, such as the placenta. Embryonic stem cells (ESCs) are an example. ESCs are derived from the inner cell mass of preimplantation embryos. Another example is induced pluripotent stem cells (iPSCs) derived from the epiblast layer of implanted embryos. Their pluripotency is a continuum, starting from completely pluripotent cells such as ESCs and iPSCs and ending on representatives with less potency—multi-, oligo- or unipotent cells. One of the methods to assess their activity and spectrum is the teratoma formation assay. iPSCs are artificially generated from somatic cells, and they function similarly to PSCs. Their culturing and utilization are very promising for present and future regenerative medicine.

Multipotent stem cells have a narrower spectrum of differentiation than PSCs, but they can specialize in discrete cells of specific cell lineages. One example is a haematopoietic stem cell, which can develop into several types of blood cells. After differentiation, a haematopoietic stem cell becomes an oligopotent cell. Its differentiation abilities are then restricted to cells of its lineage. However, some multipotent cells are capable of conversion into unrelated cell types, which suggests naming them pluripotent cells.

Oligopotent stem cells can differentiate into several cell types. A myeloid stem cell is an example that can divide into white blood cells but not red blood cells.

Unipotent stem cells are characterized by the narrowest differentiation capabilities and a special property of dividing repeatedly. Their latter feature makes them a promising candidate for therapeutic use in regenerative medicine. These cells are only able to form one cell type, e.g. dermatocytes.

Stem cell biology

A blastocyst is formed after the fusion of sperm and ovum fertilization. Its inner wall is lined with short-lived stem cells, namely, embryonic stem cells. Blastocysts are composed of two distinct cell types: the inner cell mass (ICM), which develops into epiblasts and induces the development of a foetus, and the trophectoderm (TE). Blastocysts are responsible for the regulation of the ICM microenvironment. The TE continues to develop and forms the extraembryonic support structures needed for the successful origin of the embryo, such as the placenta. As the TE begins to form a specialized support structure, the ICM cells remain undifferentiated, fully pluripotent and proliferative [ 1 ]. The pluripotency of stem cells allows them to form any cell of the organism. Human embryonic stem cells (hESCs) are derived from the ICM. During the process of embryogenesis, cells form aggregations called germ layers: endoderm, mesoderm and ectoderm (Fig.  1 ), each eventually giving rise to differentiated cells and tissues of the foetus and, later on, the adult organism [ 2 ]. After hESCs differentiate into one of the germ layers, they become multipotent stem cells, whose potency is limited to only the cells of the germ layer. This process is short in human development. After that, pluripotent stem cells occur all over the organism as undifferentiated cells, and their key abilities are proliferation by the formation of the next generation of stem cells and differentiation into specialized cells under certain physiological conditions.

Oocyte development and formation of stem cells: the blastocoel, which is formed from oocytes, consists of embryonic stem cells that later differentiate into mesodermal, ectodermal, or endodermal cells. Blastocoel develops into the gastrula

Signals that influence the stem cell specialization process can be divided into external, such as physical contact between cells or chemical secretion by surrounding tissue, and internal, which are signals controlled by genes in DNA.

Stem cells also act as internal repair systems of the body. The replenishment and formation of new cells are unlimited as long as an organism is alive. Stem cell activity depends on the organ in which they are in; for example, in bone marrow, their division is constant, although in organs such as the pancreas, division only occurs under special physiological conditions.

Stem cell functional division

Whole-body development.

During division, the presence of different stem cells depends on organism development. Somatic stem cell ESCs can be distinguished. Although the derivation of ESCs without separation from the TE is possible, such a combination has growth limits. Because proliferating actions are limited, co-culture of these is usually avoided.

ESCs are derived from the inner cell mass of the blastocyst, which is a stage of pre-implantation embryo ca. 4 days after fertilization. After that, these cells are placed in a culture dish filled with culture medium. Passage is an inefficient but popular process of sub-culturing cells to other dishes. These cells can be described as pluripotent because they are able to eventually differentiate into every cell type in the organism. Since the beginning of their studies, there have been ethical restrictions connected to the medical use of ESCs in therapies. Most embryonic stem cells are developed from eggs that have been fertilized in an in vitro clinic, not from eggs fertilized in vivo.

Somatic or adult stem cells are undifferentiated and found among differentiated cells in the whole body after development. The function of these cells is to enable the healing, growth, and replacement of cells that are lost each day. These cells have a restricted range of differentiation options. Among many types, there are the following:

Mesenchymal stem cells are present in many tissues. In bone marrow, these cells differentiate mainly into the bone, cartilage, and fat cells. As stem cells, they are an exception because they act pluripotently and can specialize in the cells of any germ layer.

Neural cells give rise to nerve cells and their supporting cells—oligodendrocytes and astrocytes.

Haematopoietic stem cells form all kinds of blood cells: red, white, and platelets.

Skin stem cells form, for example, keratinocytes, which form a protective layer of skin.

The proliferation time of somatic stem cells is longer than that of ESCs. It is possible to reprogram adult stem cells back to their pluripotent state. This can be performed by transferring the adult nucleus into the cytoplasm of an oocyte or by fusion with the pluripotent cell. The same technique was used during cloning of the famous Dolly sheep.

hESCs are involved in whole-body development. They can differentiate into pluripotent, totipotent, multipotent, and unipotent cells (Fig.  2 ) [ 2 ].

Changes in the potency of stem cells in human body development. Potency ranges from pluripotent cells of the blastocyst to unipotent cells of a specific tissue in a human body such as the skin, CNS, or bone marrow. Reversed pluripotency can be achieved by the formation of induced pluripotent stem cells using either octamer-binding transcription factor (Oct4), sex-determining region Y (Sox2), Kruppel-like factor 4 (Klf4), or the Myc gene

Pluripotent cells can be named totipotent if they can additionally form extraembryonic tissues of the embryo. Multipotent cells are restricted in differentiating to each cell type of given tissue. When tissue contains only one lineage of cells, stem cells that form them are called either called oligo- or unipotent.

iPSC quality control and recognition by morphological differences

The comparability of stem cell lines from different individuals is needed for iPSC lines to be used in therapeutics [ 3 ]. Among critical quality procedures, the following can be distinguished:

Short tandem repeat analysis—This is the comparison of specific loci on the DNA of the samples. It is used in measuring an exact number of repeating units. One unit consists of 2 to 13 nucleotides repeating many times on the DNA strand. A polymerase chain reaction is used to check the lengths of short tandem repeats. The genotyping procedure of source tissue, cells, and iPSC seed and master cell banks is recommended.

Identity analysis—The unintentional switching of lines, resulting in other stem cell line contamination, requires rigorous assay for cell line identification.

Residual vector testing—An appearance of reprogramming vectors integrated into the host genome is hazardous, and testing their presence is a mandatory procedure. It is a commonly used procedure for generating high-quality iPSC lines. An acceptable threshold in high-quality research-grade iPSC line collections is ≤ 1 plasmid copies per 100 cells. During the procedure, 2 different regions, common to all plasmids, should be used as specific targets, such as EBNA and CAG sequences [ 3 ]. To accurately represent the test reactions, a standard curve needs to be prepared in a carrier of gDNA from a well-characterized hPSC line. For calculations of plasmid copies per cell, it is crucial to incorporate internal reference gDNA sequences to allow the quantification of, for example, ribonuclease P (RNaseP) or human telomerase reverse transcriptase (hTERT).

Karyotype—A long-term culture of hESCs can accumulate culture-driven mutations [ 4 ]. Because of that, it is crucial to pay additional attention to genomic integrity. Karyotype tests can be performed by resuscitating representative aliquots and culturing them for 48–72 h before harvesting cells for karyotypic analysis. If abnormalities are found within the first 20 karyotypes, the analysis must be repeated on a fresh sample. When this situation is repeated, the line is evaluated as abnormal. Repeated abnormalities must be recorded. Although karyology is a crucial procedure in stem cell quality control, the single nucleotide polymorphism (SNP) array, discussed later, has approximately 50 times higher resolution.

Viral testing—When assessing the quality of stem cells, all tests for harmful human adventitious agents must be performed (e.g. hepatitis C or human immunodeficiency virus). This procedure must be performed in the case of non-xeno-free culture agents.

Bacteriology—Bacterial or fungal sterility tests can be divided into culture- or broth-based tests. All the procedures must be recommended by pharmacopoeia for the jurisdiction in which the work is performed.

Single nucleotide polymorphism arrays—This procedure is a type of DNA microarray that detects population polymorphisms by enabling the detection of subchromosomal changes and the copy-neutral loss of heterozygosity, as well as an indication of cellular transformation. The SNP assay consists of three components. The first is labelling fragmented nucleic acid sequences with fluorescent dyes. The second is an array that contains immobilized allele-specific oligonucleotide (ASO) probes. The last component detects, records, and eventually interprets the signal.

Flow cytometry—This is a technique that utilizes light to count and profile cells in a heterogeneous fluid mixture. It allows researchers to accurately and rapidly collect data from heterogeneous fluid mixtures with live cells. Cells are passed through a narrow channel one by one. During light illumination, sensors detect light emitted or refracted from the cells. The last step is data analysis, compilation and integration into a comprehensive picture of the sample.

Phenotypic pluripotency assays—Recognizing undifferentiated cells is crucial in successful stem cell therapy. Among other characteristics, stem cells appear to have a distinct morphology with a high nucleus to cytoplasm ratio and a prominent nucleolus. Cells appear to be flat with defined borders, in contrast to differentiating colonies, which appear as loosely located cells with rough borders [ 5 ]. It is important that images of ideal and poor quality colonies for each cell line are kept in laboratories, so whenever there is doubt about the quality of culture, it can always be checked according to the representative image. Embryoid body formation or directed differentiation of monolayer cultures to produce cell types representative of all three embryonic germ layers must be performed. It is important to note that colonies cultured under different conditions may have different morphologies [ 6 ].

Histone modification and DNA methylation—Quality control can be achieved by using epigenetic analysis tools such as histone modification or DNA methylation. When stem cells differentiate, the methylation process silences pluripotency genes, which reduces differentiation potential, although other genes may undergo demethylation to become expressed [ 7 ]. It is important to emphasize that stem cell identity, together with its morphological characteristics, is also related to its epigenetic profile [ 8 , 9 ]. According to Brindley [ 10 ], there is a relationship between epigenetic changes, pluripotency, and cell expansion conditions, which emphasizes that unmethylated regions appear to be serum-dependent.

hESC derivation and media

hESCs can be derived using a variety of methods, from classic culturing to laser-assisted methodologies or microsurgery [ 11 ]. hESC differentiation must be specified to avoid teratoma formation (see Fig.  3 ).

Spontaneous differentiation of hESCs causes the formation of a heterogeneous cell population. There is a different result, however, when commitment signals (in forms of soluble factors and culture conditions) are applied and enable the selection of progenitor cells

hESCs spontaneously differentiate into embryonic bodies (EBs) [ 12 ]. EBs can be studied instead of embryos or animals to predict their effects on early human development. There are many different methods for acquiring EBs, such as bioreactor culture [ 13 ], hanging drop culture [ 12 ], or microwell technology [ 14 , 15 ]. These methods allow specific precursors to form in vitro [ 16 ].

The essential part of these culturing procedures is a separation of inner cell mass to culture future hESCs (Fig.  4 ) [ 17 ]. Rosowski et al. [ 18 ] emphasizes that particular attention must be taken in controlling spontaneous differentiation. When the colony reaches the appropriate size, cells must be separated. The occurrence of pluripotent cells lasts for 1–2 days. Because the classical utilization of hESCs caused ethical concerns about gastrulas used during procedures, Chung et al. [ 19 ] found out that it is also possible to obtain hESCs from four cell embryos, leaving a higher probability of embryo survival. Additionally, Zhang et al. [ 20 ] used only in vitro fertilization growth-arrested cells.

Culturing of pluripotent stem cells in vitro. Three days after fertilization, totipotent cells are formed. Blastocysts with ICM are formed on the sixth day after fertilization. Pluripotent stem cells from ICM can then be successfully transmitted on a dish

Cell passaging is used to form smaller clusters of cells on a new culture surface [ 21 ]. There are four important passaging procedures.

Enzymatic dissociation is a cutting action of enzymes on proteins and adhesion domains that bind the colony. It is a gentler method than the manual passage. It is crucial to not leave hESCs alone after passaging. Solitary cells are more sensitive and can easily undergo cell death; collagenase type IV is an example [ 22 , 23 ].

Manual passage , on the other hand, focuses on using cell scratchers. The selection of certain cells is not necessary. This should be done in the early stages of cell line derivation [ 24 ].

Trypsin utilization allows a healthy, automated hESC passage. Good Manufacturing Practice (GMP)-grade recombinant trypsin is widely available in this procedure [ 24 ]. However, there is a risk of decreasing the pluripotency and viability of stem cells [ 25 ]. Trypsin utilization can be halted with an inhibitor of the protein rho-associated protein kinase (ROCK) [ 26 ].

Ethylenediaminetetraacetic acid ( EDTA ) indirectly suppresses cell-to-cell connections by chelating divalent cations. Their suppression promotes cell dissociation [ 27 ].

Stem cells require a mixture of growth factors and nutrients to differentiate and develop. The medium should be changed each day.

Traditional culture methods used for hESCs are mouse embryonic fibroblasts (MEFs) as a feeder layer and bovine serum [ 28 ] as a medium. Martin et al. [ 29 ] demonstrated that hESCs cultured in the presence of animal products express the non-human sialic acid, N -glycolylneuraminic acid (NeuGc). Feeder layers prevent uncontrolled proliferation with factors such as leukaemia inhibitory factor (LIF) [ 30 ].

First feeder layer-free culture can be supplemented with serum replacement, combined with laminin [ 31 ]. This causes stable karyotypes of stem cells and pluripotency lasting for over a year.

Initial culturing media can be serum (e.g. foetal calf serum FCS), artificial replacement such as synthetic serum substitute (SSS), knockout serum replacement (KOSR), or StemPro [ 32 ]. The simplest culture medium contains only eight essential elements: DMEM/F12 medium, selenium, NaHCO 3, l -ascorbic acid, transferrin, insulin, TGFβ1, and FGF2 [ 33 ]. It is not yet fully known whether culture systems developed for hESCs can be allowed without adaptation in iPSC cultures.

Turning point in stem cell therapy

The turning point in stem cell therapy appeared in 2006, when scientists Shinya Yamanaka, together with Kazutoshi Takahashi, discovered that it is possible to reprogram multipotent adult stem cells to the pluripotent state. This process avoided endangering the foetus’ life in the process. Retrovirus-mediated transduction of mouse fibroblasts with four transcription factors (Oct-3/4, Sox2, KLF4, and c-Myc) [ 34 ] that are mainly expressed in embryonic stem cells could induce the fibroblasts to become pluripotent (Fig.  5 ) [ 35 ]. This new form of stem cells was named iPSCs. One year later, the experiment also succeeded with human cells [ 36 ]. After this success, the method opened a new field in stem cell research with a generation of iPSC lines that can be customized and biocompatible with the patient. Recently, studies have focused on reducing carcinogenesis and improving the conduction system.

Retroviral-mediated transduction induces pluripotency in isolated patient somatic cells. Target cells lose their role as somatic cells and, once again, become pluripotent and can differentiate into any cell type of human body

The turning point was influenced by former discoveries that happened in 1962 and 1987.

The former discovery was about scientist John Gurdon successfully cloning frogs by transferring a nucleus from a frog’s somatic cells into an oocyte. This caused a complete reversion of somatic cell development [ 37 ]. The results of his experiment became an immense discovery since it was previously believed that cell differentiation is a one-way street only, but his experiment suggested the opposite and demonstrated that it is even possible for a somatic cell to again acquire pluripotency [ 38 ].

The latter was a discovery made by Davis R.L. that focused on fibroblast DNA subtraction. Three genes were found that originally appeared in myoblasts. The enforced expression of only one of the genes, named myogenic differentiation 1 (Myod1), caused the conversion of fibroblasts into myoblasts, showing that reprogramming cells is possible, and it can even be used to transform cells from one lineage to another [ 39 ].

Although pluripotency can occur naturally only in embryonic stem cells, it is possible to induce terminally differentiated cells to become pluripotent again. The process of direct reprogramming converts differentiated somatic cells into iPSC lines that can form all cell types of an organism. Reprogramming focuses on the expression of oncogenes such as Myc and Klf4 (Kruppel-like factor 4). This process is enhanced by a downregulation of genes promoting genome stability, such as p53. Additionally, cell reprogramming involves histone alteration. All these processes can cause potential mutagenic risk and later lead to an increased number of mutations. Quinlan et al. [ 40 ] checked fully pluripotent mouse iPSCs using whole genome DNA sequencing and structural variation (SV) detection algorithms. Based on those studies, it was confirmed that although there were single mutations in the non-genetic region, there were non-retrotransposon insertions. This led to the conclusion that current reprogramming methods can produce fully pluripotent iPSCs without severe genomic alterations.

During the course of development from pluripotent hESCs to differentiated somatic cells, crucial changes appear in the epigenetic structure of these cells. There is a restriction or permission of the transcription of genes relevant to each cell type. When somatic cells are being reprogrammed using transcription factors, all the epigenetic architecture has to be reconditioned to achieve iPSCs with pluripotency [ 41 ]. However, cells of each tissue undergo specific somatic genomic methylation. This influences transcription, which can further cause alterations in induced pluripotency [ 42 ].

Source of iPSCs

Because pluripotent cells can propagate indefinitely and differentiate into any kind of cell, they can be an unlimited source, either for replacing lost or diseased tissues. iPSCs bypass the need for embryos in stem cell therapy. Because they are made from the patient’s own cells, they are autologous and no longer generate any risk of immune rejection.

At first, fibroblasts were used as a source of iPSCs. Because a biopsy was needed to achieve these types of cells, the technique underwent further research. Researchers investigated whether more accessible cells could be used in the method. Further, other cells were used in the process: peripheral blood cells, keratinocytes, and renal epithelial cells found in urine. An alternative strategy to stem cell transplantation can be stimulating a patient’s endogenous stem cells to divide or differentiate, occurring naturally when skin wounds are healing. In 2008, pancreatic exocrine cells were shown to be reprogrammed to functional, insulin-producing beta cells [ 43 ].

The best stem cell source appears to be the fibroblasts, which is more tempting in the case of logistics since its stimulation can be fast and better controlled [ 44 ].

• Teratoma formation assay

The self-renewal and differentiation capabilities of iPSCs have gained significant interest and attention in regenerative medicine sciences. To study their abilities, a quality-control assay is needed, of which one of the most important is the teratoma formation assay. Teratomas are benign tumours. Teratomas are capable of rapid growth in vivo and are characteristic because of their ability to develop into tissues of all three germ layers simultaneously. Because of the high pluripotency of teratomas, this formation assay is considered an assessment of iPSC’s abilities [ 45 ].

Teratoma formation rate, for instance, was observed to be elevated in human iPSCs compared to that in hESCs [ 46 ]. This difference may be connected to different differentiation methods and cell origins. Most commonly, the teratoma assay involves an injection of examined iPSCs subcutaneously or under the testis or kidney capsule in mice, which are immune-deficient [ 47 ]. After injection, an immature but recognizable tissue can be observed, such as the kidney tubules, bone, cartilage, or neuroepithelium [ 30 ]. The injection site may have an impact on the efficiency of teratoma formation [ 48 ].

There are three groups of markers used in this assay to differentiate the cells of germ layers. For endodermal tissue, there is insulin/C-peptide and alpha-1 antitrypsin [ 49 ]. For the mesoderm, derivatives can be used, e.g. cartilage matrix protein for the bone and alcian blue for the cartilage. As ectodermal markers, class III B botulin or keratin can be used for keratinocytes.

Teratoma formation assays are considered the gold standard for demonstrating the pluripotency of human iPSCs, demonstrating their possibilities under physiological conditions. Due to their actual tissue formation, they could be used for the characterization of many cell lineages [ 50 ].

Directed differentiation

To be useful in therapy, stem cells must be converted into desired cell types as necessary or else the whole regenerative medicine process will be pointless. Differentiation of ESCs is crucial because undifferentiated ESCs can cause teratoma formation in vivo. Understanding and using signalling pathways for differentiation is an important method in successful regenerative medicine. In directed differentiation, it is likely to mimic signals that are received by cells when they undergo successive stages of development [ 51 ]. The extracellular microenvironment plays a significant role in controlling cell behaviour. By manipulating the culture conditions, it is possible to restrict specific differentiation pathways and generate cultures that are enriched in certain precursors in vitro. However, achieving a similar effect in vivo is challenging. It is crucial to develop culture conditions that will allow the promotion of homogenous and enhanced differentiation of ESCs into functional and desired tissues.

Regarding the self-renewal of embryonic stem cells, Hwang et al. [ 52 ] noted that the ideal culture method for hESC-based cell and tissue therapy would be a defined culture free of either the feeder layer or animal components. This is because cell and tissue therapy requires the maintenance of large quantities of undifferentiated hESCs, which does not make feeder cells suitable for such tasks.

Most directed differentiation protocols are formed to mimic the development of an inner cell mass during gastrulation. During this process, pluripotent stem cells differentiate into ectodermal, mesodermal, or endodermal progenitors. Mall molecules or growth factors induce the conversion of stem cells into appropriate progenitor cells, which will later give rise to the desired cell type. There is a variety of signal intensities and molecular families that may affect the establishment of germ layers in vivo, such as fibroblast growth factors (FGFs) [ 53 ]; the Wnt family [ 54 ] or superfamily of transforming growth factors—β(TGFβ); and bone morphogenic proteins (BMP) [ 55 ]. Each candidate factor must be tested on various concentrations and additionally applied to various durations because the precise concentrations and times during which developing cells in embryos are influenced during differentiation are unknown. For instance, molecular antagonists of endogenous BMP and Wnt signalling can be used for ESC formation of ectoderm [ 56 ]. However, transient Wnt and lower concentrations of the TGFβ family trigger mesodermal differentiation [ 57 ]. Regarding endoderm formation, a higher activin A concentration may be required [ 58 , 59 ].

There are numerous protocols about the methods of forming progenitors of cells of each of germ layers, such as cardiomyocytes [ 60 ], hepatocytes [ 61 ], renal cells [ 62 ], lung cells [ 63 , 64 ], motor neurons [ 65 ], intestinal cells [ 66 ], or chondrocytes [ 67 ].

Directed differentiation of either iPSCs or ESCs into, e.g. hepatocytes, could influence and develop the study of the molecular mechanisms in human liver development. In addition, it could also provide the possibility to form exogenous hepatocytes for drug toxicity testing [ 68 ].

Levels of concentration and duration of action with a specific signalling molecule can cause a variety of factors. Unfortunately, for now, a high cost of recombinant factors is likely to limit their use on a larger scale in medicine. The more promising technique focuses on the use of small molecules. These can be used for either activating or deactivating specific signalling pathways. They enhance reprogramming efficiency by creating cells that are compatible with the desired type of tissue. It is a cheaper and non-immunogenic method.

One of the successful examples of small-molecule cell therapies is antagonists and agonists of the Hedgehog pathway. They show to be very useful in motor neuron regeneration [ 69 ]. Endogenous small molecules with their function in embryonic development can also be used in in vitro methods to induce the differentiation of cells; for example, retinoic acid, which is responsible for patterning the nervous system in vivo [ 70 ], surprisingly induced retinal cell formation when the laboratory procedure involved hESCs [ 71 ].

The efficacy of differentiation factors depends on functional maturity, efficiency, and, finally, introducing produced cells to their in vivo equivalent. Topography, shear stress, and substrate rigidity are factors influencing the phenotype of future cells [ 72 ].

The control of biophysical and biochemical signals, the biophysical environment, and a proper guide of hESC differentiation are important factors in appropriately cultured stem cells.

Stem cell utilization and their manufacturing standards and culture systems

The European Medicines Agency and the Food and Drug Administration have set Good Manufacturing Practice (GMP) guidelines for safe and appropriate stem cell transplantation. In the past, protocols used for stem cell transplantation required animal-derived products [ 73 ].

The risk of introducing animal antigens or pathogens caused a restriction in their use. Due to such limitations, the technique required an obvious update [ 74 ]. Now, it is essential to use xeno-free equivalents when establishing cell lines that are derived from fresh embryos and cultured from human feeder cell lines [ 75 ]. In this method, it is crucial to replace any non-human materials with xeno-free equivalents [ 76 ].

NutriStem with LN-511, TeSR2 with human recombinant laminin (LN-511), and RegES with human foreskin fibroblasts (HFFs) are commonly used xeno-free culture systems [ 33 ]. There are many organizations and international initiatives, such as the National Stem Cell Bank, that provide stem cell lines for treatment or medical research [ 77 ].

Stem cell use in medicine

Stem cells have great potential to become one of the most important aspects of medicine. In addition to the fact that they play a large role in developing restorative medicine, their study reveals much information about the complex events that happen during human development.

The difference between a stem cell and a differentiated cell is reflected in the cells’ DNA. In the former cell, DNA is arranged loosely with working genes. When signals enter the cell and the differentiation process begins, genes that are no longer needed are shut down, but genes required for the specialized function will remain active. This process can be reversed, and it is known that such pluripotency can be achieved by interaction in gene sequences. Takahashi and Yamanaka [ 78 ] and Loh et al. [ 79 ] discovered that octamer-binding transcription factor 3 and 4 (Oct3/4), sex determining region Y (SRY)-box 2 and Nanog genes function as core transcription factors in maintaining pluripotency. Among them, Oct3/4 and Sox2 are essential for the generation of iPSCs.

Many serious medical conditions, such as birth defects or cancer, are caused by improper differentiation or cell division. Currently, several stem cell therapies are possible, among which are treatments for spinal cord injury, heart failure [ 80 ], retinal and macular degeneration [ 81 ], tendon ruptures, and diabetes type 1 [ 82 ]. Stem cell research can further help in better understanding stem cell physiology. This may result in finding new ways of treating currently incurable diseases.

Haematopoietic stem cell transplantation

Haematopoietic stem cells are important because they are by far the most thoroughly characterized tissue-specific stem cell; after all, they have been experimentally studied for more than 50 years. These stem cells appear to provide an accurate paradigm model system to study tissue-specific stem cells, and they have potential in regenerative medicine.

Multipotent haematopoietic stem cell (HSC) transplantation is currently the most popular stem cell therapy. Target cells are usually derived from the bone marrow, peripheral blood, or umbilical cord blood [ 83 ]. The procedure can be autologous (when the patient’s own cells are used), allogenic (when the stem cell comes from a donor), or syngeneic (from an identical twin). HSCs are responsible for the generation of all functional haematopoietic lineages in blood, including erythrocytes, leukocytes, and platelets. HSC transplantation solves problems that are caused by inappropriate functioning of the haematopoietic system, which includes diseases such as leukaemia and anaemia. However, when conventional sources of HSC are taken into consideration, there are some important limitations. First, there is a limited number of transplantable cells, and an efficient way of gathering them has not yet been found. There is also a problem with finding a fitting antigen-matched donor for transplantation, and viral contamination or any immunoreactions also cause a reduction in efficiency in conventional HSC transplantations. Haematopoietic transplantation should be reserved for patients with life-threatening diseases because it has a multifactorial character and can be a dangerous procedure. iPSC use is crucial in this procedure. The use of a patient’s own unspecialized somatic cells as stem cells provides the greatest immunological compatibility and significantly increases the success of the procedure.

Stem cells as a target for pharmacological testing

Stem cells can be used in new drug tests. Each experiment on living tissue can be performed safely on specific differentiated cells from pluripotent cells. If any undesirable effect appears, drug formulas can be changed until they reach a sufficient level of effectiveness. The drug can enter the pharmacological market without harming any live testers. However, to test the drugs properly, the conditions must be equal when comparing the effects of two drugs. To achieve this goal, researchers need to gain full control of the differentiation process to generate pure populations of differentiated cells.

Stem cells as an alternative for arthroplasty

One of the biggest fears of professional sportsmen is getting an injury, which most often signifies the end of their professional career. This applies especially to tendon injuries, which, due to current treatment options focusing either on conservative or surgical treatment, often do not provide acceptable outcomes. Problems with the tendons start with their regeneration capabilities. Instead of functionally regenerating after an injury, tendons merely heal by forming scar tissues that lack the functionality of healthy tissues. Factors that may cause this failed healing response include hypervascularization, deposition of calcific materials, pain, or swelling [ 84 ].

Additionally, in addition to problems with tendons, there is a high probability of acquiring a pathological condition of joints called osteoarthritis (OA) [ 85 ]. OA is common due to the avascular nature of articular cartilage and its low regenerative capabilities [ 86 ]. Although arthroplasty is currently a common procedure in treating OA, it is not ideal for younger patients because they can outlive the implant and will require several surgical procedures in the future. These are situations where stem cell therapy can help by stopping the onset of OA [ 87 ]. However, these procedures are not well developed, and the long-term maintenance of hyaline cartilage requires further research.

Osteonecrosis of the femoral hip (ONFH) is a refractory disease associated with the collapse of the femoral head and risk of hip arthroplasty in younger populations [ 88 ]. Although total hip arthroplasty (THA) is clinically successful, it is not ideal for young patients, mostly due to the limited lifetime of the prosthesis. An increasing number of clinical studies have evaluated the therapeutic effect of stem cells on ONFH. Most of the authors demonstrated positive outcomes, with reduced pain, improved function, or avoidance of THA [ 89 , 90 , 91 ].

Rejuvenation by cell programming

Ageing is a reversible epigenetic process. The first cell rejuvenation study was published in 2011 [ 92 ]. Cells from aged individuals have different transcriptional signatures, high levels of oxidative stress, dysfunctional mitochondria, and shorter telomeres than in young cells [ 93 ]. There is a hypothesis that when human or mouse adult somatic cells are reprogrammed to iPSCs, their epigenetic age is virtually reset to zero [ 94 ]. This was based on an epigenetic model, which explains that at the time of fertilization, all marks of parenteral ageing are erased from the zygote’s genome and its ageing clock is reset to zero [ 95 ].

In their study, Ocampo et al. [ 96 ] used Oct4, Sox2, Klf4, and C-myc genes (OSKM genes) and affected pancreas and skeletal muscle cells, which have poor regenerative capacity. Their procedure revealed that these genes can also be used for effective regenerative treatment [ 97 ]. The main challenge of their method was the need to employ an approach that does not use transgenic animals and does not require an indefinitely long application. The first clinical approach would be preventive, focused on stopping or slowing the ageing rate. Later, progressive rejuvenation of old individuals can be attempted. In the future, this method may raise some ethical issues, such as overpopulation, leading to lower availability of food and energy.

For now, it is important to learn how to implement cell reprogramming technology in non-transgenic elder animals and humans to erase marks of ageing without removing the epigenetic marks of cell identity.

Cell-based therapies

Stem cells can be induced to become a specific cell type that is required to repair damaged or destroyed tissues (Fig.  6 ). Currently, when the need for transplantable tissues and organs outweighs the possible supply, stem cells appear to be a perfect solution for the problem. The most common conditions that benefit from such therapy are macular degenerations [ 98 ], strokes [ 99 ], osteoarthritis [ 89 , 90 ], neurodegenerative diseases, and diabetes [ 100 ]. Due to this technique, it can become possible to generate healthy heart muscle cells and later transplant them to patients with heart disease.

Stem cell experiments on animals. These experiments are one of the many procedures that proved stem cells to be a crucial factor in future regenerative medicine

In the case of type 1 diabetes, insulin-producing cells in the pancreas are destroyed due to an autoimmunological reaction. As an alternative to transplantation therapy, it can be possible to induce stem cells to differentiate into insulin-producing cells [ 101 ].

Stem cells and tissue banks

iPS cells with their theoretically unlimited propagation and differentiation abilities are attractive for the present and future sciences. They can be stored in a tissue bank to be an essential source of human tissue used for medical examination. The problem with conventional differentiated tissue cells held in the laboratory is that their propagation features diminish after time. This does not occur in iPSCs.

The umbilical cord is known to be rich in mesenchymal stem cells. Due to its cryopreservation immediately after birth, its stem cells can be successfully stored and used in therapies to prevent the future life-threatening diseases of a given patient.

Stem cells of human exfoliated deciduous teeth (SHED) found in exfoliated deciduous teeth has the ability to develop into more types of body tissues than other stem cells [ 102 ] (Table  1 ). Techniques of their collection, isolation, and storage are simple and non-invasive. Among the advantages of banking, SHED cells are:

Guaranteed donor-match autologous transplant that causes no immune reaction and rejection of cells [ 103 ]

Simple and painless for both child and parent

Less than one third of the cost of cord blood storage

Not subject to the same ethical concerns as embryonic stem cells [ 104 ]

In contrast to cord blood stem cells, SHED cells are able to regenerate into solid tissues such as connective, neural, dental, or bone tissue [ 105 , 106 ]

SHED can be useful for close relatives of the donor

Fertility diseases

In 2011, two researchers, Katsuhiko Hayashi et al. [ 107 ], showed in an experiment on mice that it is possible to form sperm from iPSCs. They succeeded in delivering healthy and fertile pups in infertile mice. The experiment was also successful for female mice, where iPSCs formed fully functional eggs .

Young adults at risk of losing their spermatogonial stem cells (SSC), mostly cancer patients, are the main target group that can benefit from testicular tissue cryopreservation and autotransplantation. Effective freezing methods for adult and pre-pubertal testicular tissue are available [ 108 ].

Qiuwan et al. [ 109 ] provided important evidence that human amniotic epithelial cell (hAEC) transplantation could effectively improve ovarian function by inhibiting cell apoptosis and reducing inflammation in injured ovarian tissue of mice, and it could be a promising strategy for the management of premature ovarian failure or insufficiency in female cancer survivors.

For now, reaching successful infertility treatments in humans appears to be only a matter of time, but there are several challenges to overcome. First, the process needs to have high efficiency; second, the chances of forming tumours instead of eggs or sperm must be maximally reduced. The last barrier is how to mature human sperm and eggs in the lab without transplanting them to in vivo conditions, which could cause either a tumour risk or an invasive procedure.

Therapy for incurable neurodegenerative diseases

Thanks to stem cell therapy, it is possible not only to delay the progression of incurable neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease (AD), and Huntington disease, but also, most importantly, to remove the source of the problem. In neuroscience, the discovery of neural stem cells (NSCs) has nullified the previous idea that adult CNS were not capable of neurogenesis [ 110 , 111 ]. Neural stem cells are capable of improving cognitive function in preclinical rodent models of AD [ 112 , 113 , 114 ]. Awe et al. [ 115 ] clinically derived relevant human iPSCs from skin punch biopsies to develop a neural stem cell-based approach for treating AD. Neuronal degeneration in Parkinson’s disease (PD) is focal, and dopaminergic neurons can be efficiently generated from hESCs. PD is an ideal disease for iPSC-based cell therapy [ 116 ]. However, this therapy is still in an experimental phase ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539501 /). Brain tissue from aborted foetuses was used on patients with Parkinson’s disease [ 117 ]. Although the results were not uniform, they showed that therapies with pure stem cells are an important and achievable therapy.

Stem cell use in dentistry

Teeth represent a very challenging material for regenerative medicine. They are difficult to recreate because of their function in aspects such as articulation, mastication, or aesthetics due to their complicated structure. Currently, there is a chance for stem cells to become more widely used than synthetic materials. Teeth have a large advantage of being the most natural and non-invasive source of stem cells.

For now, without the use of stem cells, the most common periodontological treatments are either growth factors, grafts, or surgery. For example, there are stem cells in periodontal ligament [ 118 , 119 ], which are capable of differentiating into osteoblasts or cementoblasts, and their functions were also assessed in neural cells [ 120 ]. Tissue engineering is a successful method for treating periodontal diseases. Stem cells of the root apical areas are able to recreate periodontal ligament. One of the possible methods of tissue engineering in periodontology is gene therapy performed using adenoviruses-containing growth factors [ 121 ].

As a result of animal studies, dentin regeneration is an effective process that results in the formation of dentin bridges [ 122 ].

Enamel is more difficult to regenerate than dentin. After the differentiation of ameloblastoma cells into the enamel, the former is destroyed, and reparation is impossible. Medical studies have succeeded in differentiating bone marrow stem cells into ameloblastoma [ 123 ].

Healthy dental tissue has a high amount of regular stem cells, although this number is reduced when tissue is either traumatized or inflamed [ 124 ]. There are several dental stem cell groups that can be isolated (Fig.  7 ).

Localization of stem cells in dental tissues. Dental pulp stem cells (DPSCs) and human deciduous teeth stem cells (SHED) are located in the dental pulp. Periodontal ligaments stem cells are located in the periodontal ligament. Apical papilla consists of stem cells from the apical papilla (SCAP)

Dental pulp stem cell (DPSC)

These were the first dental stem cells isolated from the human dental pulp, which were [ 125 ] located inside dental pulp (Table  2 ). They have osteogenic and chondrogenic potential. Mesenchymal stem cells (MSCs) of the dental pulp, when isolated, appear highly clonogenic; they can be isolated from adult tissue (e.g. bone marrow, adipose tissue) and foetal (e.g. umbilical cord) [ 126 ] tissue, and they are able to differentiate densely [ 127 ]. MSCs differentiate into odontoblast-like cells and osteoblasts to form dentin and bone. Their best source locations are the third molars [ 125 ]. DPSCs are the most useful dental source of tissue engineering due to their easy surgical accessibility, cryopreservation possibility, increased production of dentin tissues compared to non-dental stem cells, and their anti-inflammatory abilities. These cells have the potential to be a source for maxillofacial and orthopaedic reconstructions or reconstructions even beyond the oral cavity. DPSCs are able to generate all structures of the developed tooth [ 128 ]. In particular, beneficial results in the use of DPSCs may be achieved when combined with other new therapies, such as periodontal tissue photobiomodulation (laser stimulation), which is an efficient technique in the stimulation of proliferation and differentiation into distinct cell types [ 129 ]. DPSCs can be induced to form neural cells to help treat neurological deficits.

Stem cells of human exfoliated deciduous teeth (SHED) have a faster rate of proliferation than DPSCs and differentiate into an even greater number of cells, e.g. other mesenchymal and non-mesenchymal stem cell derivatives, such as neural cells [ 130 ]. These cells possess one major disadvantage: they form a non-complete dentin/pulp-like complex in vivo. SHED do not undergo the same ethical concerns as embryonic stem cells. Both DPSCs and SHED are able to form bone-like tissues in vivo [ 131 ] and can be used for periodontal, dentin, or pulp regeneration. DPSCs and SHED can be used in treating, for example, neural deficits [ 132 ]. DPSCs alone were tested and successfully applied for alveolar bone and mandible reconstruction [ 133 ].

Periodontal ligament stem cells (PDLSCs)

These cells are used in periodontal ligament or cementum tissue regeneration. They can differentiate into mesenchymal cell lineages to produce collagen-forming cells, adipocytes, cementum tissue, Sharpey’s fibres, and osteoblast-like cells in vitro. PDLSCs exist both on the root and alveolar bone surfaces; however, on the latter, these cells have better differentiation abilities than on the former [ 134 ]. PDLSCs have become the first treatment for periodontal regeneration therapy because of their safety and efficiency [ 135 , 136 ].

Stem cells from apical papilla (SCAP)

These cells are mesenchymal structures located within immature roots. They are isolated from human immature permanent apical papilla. SCAP are the source of odontoblasts and cause apexogenesis. These stem cells can be induced in vitro to form odontoblast-like cells, neuron-like cells, or adipocytes. SCAP have a higher capacity of proliferation than DPSCs, which makes them a better choice for tissue regeneration [ 137 , 138 ].

Dental follicle stem cells (DFCs)

These cells are loose connective tissues surrounding the developing tooth germ. DFCs contain cells that can differentiate into cementoblasts, osteoblasts, and periodontal ligament cells [ 139 , 140 ]. Additionally, these cells proliferate after even more than 30 passages [ 141 ]. DFCs are most commonly extracted from the sac of a third molar. When DFCs are combined with a treated dentin matrix, they can form a root-like tissue with a pulp-dentin complex and eventually form tooth roots [ 141 ]. When DFC sheets are induced by Hertwig’s epithelial root sheath cells, they can produce periodontal tissue; thus, DFCs represent a very promising material for tooth regeneration [ 142 ].

Pulp regeneration in endodontics

Dental pulp stem cells can differentiate into odontoblasts. There are few methods that enable the regeneration of the pulp.

The first is an ex vivo method. Proper stem cells are grown on a scaffold before they are implanted into the root channel [ 143 ].

The second is an in vivo method. This method focuses on injecting stem cells into disinfected root channels after the opening of the in vivo apex. Additionally, the use of a scaffold is necessary to prevent the movement of cells towards other tissues. For now, only pulp-like structures have been created successfully.

Methods of placing stem cells into the root channel constitute are either soft scaffolding [ 144 ] or the application of stem cells in apexogenesis or apexification. Immature teeth are the best source [ 145 ]. Nerve and blood vessel network regeneration are extremely vital to keep pulp tissue healthy.

The potential of dental stem cells is mainly regarding the regeneration of damaged dentin and pulp or the repair of any perforations; in the future, it appears to be even possible to generate the whole tooth. Such an immense success would lead to the gradual replacement of implant treatments. Mandibulary and maxillary defects can be one of the most complicated dental problems for stem cells to address.

Acquiring non-dental tissue cells by dental stem cell differentiation

In 2013, it was reported that it is possible to grow teeth from stem cells obtained extra-orally, e.g. from urine [ 146 ]. Pluripotent stem cells derived from human urine were induced and generated tooth-like structures. The physical properties of the structures were similar to natural ones except for hardness [ 127 ]. Nonetheless, it appears to be a very promising technique because it is non-invasive and relatively low-cost, and somatic cells can be used instead of embryonic cells. More importantly, stem cells derived from urine did not form any tumours, and the use of autologous cells reduces the chances of rejection [ 147 ].

Use of graphene in stem cell therapy

Over recent years, graphene and its derivatives have been increasingly used as scaffold materials to mediate stem cell growth and differentiation [ 148 ]. Both graphene and graphene oxide (GO) represent high in-plane stiffness [ 149 ]. Because graphene has carbon and aromatic network, it works either covalently or non-covalently with biomolecules; in addition to its superior mechanical properties, graphene offers versatile chemistry. Graphene exhibits biocompatibility with cells and their proper adhesion. It also tested positively for enhancing the proliferation or differentiation of stem cells [ 148 ]. After positive experiments, graphene revealed great potential as a scaffold and guide for specific lineages of stem cell differentiation [ 150 ]. Graphene has been successfully used in the transplantation of hMSCs and their guided differentiation to specific cells. The acceleration skills of graphene differentiation and division were also investigated. It was discovered that graphene can serve as a platform with increased adhesion for both growth factors and differentiation chemicals. It was also discovered that π-π binding was responsible for increased adhesion and played a crucial role in inducing hMSC differentiation [ 150 ].

Therapeutic potential of extracellular vesicle-based therapies

Extracellular vesicles (EVs) can be released by virtually every cell of an organism, including stem cells [ 151 ], and are involved in intercellular communication through the delivery of their mRNAs, lipids, and proteins. As Oh et al. [ 152 ] prove, stem cells, together with their paracrine factors—exosomes—can become potential therapeutics in the treatment of, e.g. skin ageing. Exosomes are small membrane vesicles secreted by most cells (30–120 nm in diameter) [ 153 ]. When endosomes fuse with the plasma membrane, they become exosomes that have messenger RNAs (mRNAs) and microRNAs (miRNAs), some classes of non-coding RNAs (IncRNAs) and several proteins that originate from the host cell [ 154 ]. IncRNAs can bind to specific loci and create epigenetic regulators, which leads to the formation of epigenetic modifications in recipient cells. Because of this feature, exosomes are believed to be implicated in cell-to-cell communication and the progression of diseases such as cancer [ 155 ]. Recently, many studies have also shown the therapeutic use of exosomes derived from stem cells, e.g. skin damage and renal or lung injuries [ 156 ].

In skin ageing, the most important factor is exposure to UV light, called “photoageing” [ 157 ], which causes extrinsic skin damage, characterized by dryness, roughness, irregular pigmentation, lesions, and skin cancers. In intrinsic skin ageing, on the other hand, the loss of elasticity is a characteristic feature. The skin dermis consists of fibroblasts, which are responsible for the synthesis of crucial skin elements, such as procollagen or elastic fibres. These elements form either basic framework extracellular matrix constituents of the skin dermis or play a major role in tissue elasticity. Fibroblast efficiency and abundance decrease with ageing [ 158 ]. Stem cells can promote the proliferation of dermal fibroblasts by secreting cytokines such as platelet-derived growth factor (PDGF), transforming growth factor β (TGF-β), and basic fibroblast growth factor. Huh et al. [ 159 ] mentioned that a medium of human amniotic fluid-derived stem cells (hAFSC) positively affected skin regeneration after longwave UV-induced (UVA, 315–400 nm) photoageing by increasing the proliferation and migration of dermal fibroblasts. It was discovered that, in addition to the induction of fibroblast physiology, hAFSC transplantation also improved diseases in cases of renal pathology, various cancers, or stroke [ 160 , 161 ].

Oh [ 162 ] also presented another option for the treatment of skin wounds, either caused by physical damage or due to diabetic ulcers. Induced pluripotent stem cell-conditioned medium (iPSC-CM) without any animal-derived components induced dermal fibroblast proliferation and migration.

Natural cutaneous wound healing is divided into three steps: haemostasis/inflammation, proliferation, and remodelling. During the crucial step of proliferation, fibroblasts migrate and increase in number, indicating that it is a critical step in skin repair, and factors such as iPSC-CM that impact it can improve the whole cutaneous wound healing process. Paracrine actions performed by iPSCs are also important for this therapeutic effect [ 163 ]. These actions result in the secretion of cytokines such as TGF-β, interleukin (IL)-6, IL-8, monocyte chemotactic protein-1 (MCP-1), vascular endothelial growth factor (VEGF), platelet-derived growth factor-AA (PDGF-AA), and basic fibroblast growth factor (bFGF). Bae et al. [ 164 ] mentioned that TGF-β induced the migration of keratinocytes. It was also demonstrated that iPSC factors can enhance skin wound healing in vivo and in vitro when Zhou et al. [ 165 ] enhanced wound healing, even after carbon dioxide laser resurfacing in an in vivo study.

Peng et al. [ 166 ] investigated the effects of EVs derived from hESCs on in vitro cultured retinal glial, progenitor Müller cells, which are known to differentiate into retinal neurons. EVs appear heterogeneous in size and can be internalized by cultured Müller cells, and their proteins are involved in the induction and maintenance of stem cell pluripotency. These stem cell-derived vesicles were responsible for the neuronal trans-differentiation of cultured Müller cells exposed to them. However, the research article points out that the procedure was accomplished only on in vitro acquired retina.

Challenges concerning stem cell therapy

Although stem cells appear to be an ideal solution for medicine, there are still many obstacles that need to be overcome in the future. One of the first problems is ethical concern.

The most common pluripotent stem cells are ESCs. Therapies concerning their use at the beginning were, and still are, the source of ethical conflicts. The reason behind it started when, in 1998, scientists discovered the possibility of removing ESCs from human embryos. Stem cell therapy appeared to be very effective in treating many, even previously incurable, diseases. The problem was that when scientists isolated ESCs in the lab, the embryo, which had potential for becoming a human, was destroyed (Fig.  8 ). Because of this, scientists, seeing a large potential in this treatment method, focused their efforts on making it possible to isolate stem cells without endangering their source—the embryo.

Use of inner cell mass pluripotent stem cells and their stimulation to differentiate into desired cell types

For now, while hESCs still remain an ethically debatable source of cells, they are potentially powerful tools to be used for therapeutic applications of tissue regeneration. Because of the complexity of stem cell control systems, there is still much to be learned through observations in vitro. For stem cells to become a popular and widely accessible procedure, tumour risk must be assessed. The second problem is to achieve successful immunological tolerance between stem cells and the patient’s body. For now, one of the best ideas is to use the patient’s own cells and devolve them into their pluripotent stage of development.

New cells need to have the ability to fully replace lost or malfunctioning natural cells. Additionally, there is a concern about the possibility of obtaining stem cells without the risk of morbidity or pain for either the patient or the donor. Uncontrolled proliferation and differentiation of cells after implementation must also be assessed before its use in a wide variety of regenerative procedures on living patients [ 167 ].

One of the arguments that limit the use of iPSCs is their infamous role in tumourigenicity. There is a risk that the expression of oncogenes may increase when cells are being reprogrammed. In 2008, a technique was discovered that allowed scientists to remove oncogenes after a cell achieved pluripotency, although it is not efficient yet and takes a longer amount of time. The process of reprogramming may be enhanced by deletion of the tumour suppressor gene p53, but this gene also acts as a key regulator of cancer, which makes it impossible to remove in order to avoid more mutations in the reprogrammed cell. The low efficiency of the process is another problem, which is progressively becoming reduced with each year. At first, the rate of somatic cell reprogramming in Yamanaka’s study was up to 0.1%. The use of transcription factors creates a risk of genomic insertion and further mutation of the target cell genome. For now, the only ethically acceptable operation is an injection of hESCs into mouse embryos in the case of pluripotency evaluation [ 168 ].

Stem cell obstacles in the future

Pioneering scientific and medical advances always have to be carefully policed in order to make sure they are both ethical and safe. Because stem cell therapy already has a large impact on many aspects of life, it should not be treated differently.

Currently, there are several challenges concerning stem cells. First, the most important one is about fully understanding the mechanism by which stem cells function first in animal models. This step cannot be avoided. For the widespread, global acceptance of the procedure, fear of the unknown is the greatest challenge to overcome.

The efficiency of stem cell-directed differentiation must be improved to make stem cells more reliable and trustworthy for a regular patient. The scale of the procedure is another challenge. Future stem cell therapies may be a significant obstacle. Transplanting new, fully functional organs made by stem cell therapy would require the creation of millions of working and biologically accurate cooperating cells. Bringing such complicated procedures into general, widespread regenerative medicine will require interdisciplinary and international collaboration.

The identification and proper isolation of stem cells from a patient’s tissues is another challenge. Immunological rejection is a major barrier to successful stem cell transplantation. With certain types of stem cells and procedures, the immune system may recognize transplanted cells as foreign bodies, triggering an immune reaction resulting in transplant or cell rejection.

One of the ideas that can make stem cells a “failsafe” is about implementing a self-destruct option if they become dangerous. Further development and versatility of stem cells may cause reduction of treatment costs for people suffering from currently incurable diseases. When facing certain organ failure, instead of undergoing extraordinarily expensive drug treatment, the patient would be able to utilize stem cell therapy. The effect of a successful operation would be immediate, and the patient would avoid chronic pharmacological treatment and its inevitable side effects.

Although these challenges facing stem cell science can be overwhelming, the field is making great advances each day. Stem cell therapy is already available for treating several diseases and conditions. Their impact on future medicine appears to be significant.

After several decades of experiments, stem cell therapy is becoming a magnificent game changer for medicine. With each experiment, the capabilities of stem cells are growing, although there are still many obstacles to overcome. Regardless, the influence of stem cells in regenerative medicine and transplantology is immense. Currently, untreatable neurodegenerative diseases have the possibility of becoming treatable with stem cell therapy. Induced pluripotency enables the use of a patient’s own cells. Tissue banks are becoming increasingly popular, as they gather cells that are the source of regenerative medicine in a struggle against present and future diseases. With stem cell therapy and all its regenerative benefits, we are better able to prolong human life than at any time in history.

Abbreviations

Basic fibroblast growth factor

Bone morphogenic proteins

Dental follicle stem cells

Dental pulp stem cells

Embryonic bodies

Embryonic stem cells

Fibroblast growth factors

Good Manufacturing Practice

Graphene oxide

Human amniotic fluid-derived stem cells

Human embryonic stem cells

Human foreskin fibroblasts

Inner cell mass

Non-coding RNA

Induced pluripotent stem cells

In vitro fertilization

Knockout serum replacement

Leukaemia inhibitory factor

Monocyte chemotactic protein-1

Fibroblasts

Messenger RNA

Mesenchymal stem cells of dental pulp

Myogenic differentiation

Osteoarthritis

Octamer-binding transcription factor 3 and 4

Platelet-derived growth factor

Platelet-derived growth factor-AA

Periodontal ligament stem cells

Rho-associated protein kinase

Stem cells from apical papilla

Stem cells of human exfoliated deciduous teeth

Synthetic Serum Substitute

Trophectoderm

Vascular endothelial growth factor

Transforming growth factors

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112 Stem Cell Essay Topic Ideas & Examples

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Stem cell research is a rapidly advancing field in the realm of medical science, with the potential to revolutionize the way we treat various diseases and injuries. However, with this exciting potential comes a myriad of ethical, legal, and societal implications that must be carefully considered.

If you are tasked with writing an essay on stem cells, you may be wondering where to start. To help you get your creative juices flowing, we have compiled a list of 112 stem cell essay topic ideas and examples that you can use as inspiration for your writing.

• The history of stem cell research
• Types of stem cells and their properties
• The potential applications of stem cell therapy
• The ethical considerations of using embryonic stem cells
• The role of stem cells in regenerative medicine
• The impact of stem cell research on cancer treatment
• The use of stem cells in treating neurodegenerative diseases
• The controversy surrounding cloning and stem cell research
• The role of stem cells in tissue engineering
• The potential risks and benefits of stem cell therapy
• The future of stem cell research
• The role of stem cells in personalized medicine
• The use of stem cells in treating diabetes
• The potential applications of stem cell therapy in treating heart disease
• The role of stem cells in treating spinal cord injuries
• The ethical implications of creating chimeras for research purposes
• The impact of stem cell research on the pharmaceutical industry
• The potential applications of stem cells in treating autoimmune diseases
• The role of stem cells in treating infertility
• The use of stem cells in organ transplantation
• The potential applications of stem cells in treating Alzheimer's disease
• The role of stem cells in treating Parkinson's disease
• The ethical considerations of using adult stem cells
• The impact of stem cell research on the field of genetics
• The role of stem cells in treating muscular dystrophy
• The potential applications of stem cells in treating arthritis
• The use of stem cells in treating liver disease
• The role of stem cells in treating lung disease
• The ethical implications of using induced pluripotent stem cells
• The impact of stem cell research on the field of neuroscience
• The potential applications of stem cells in treating eye diseases
• The role of stem cells in treating skin disorders
• The use of stem cells in treating kidney disease
• The potential applications of stem cells in treating bone disorders
• The role of stem cells in treating blood disorders
• The ethical considerations of using umbilical cord blood stem cells
• The impact of stem cell research on the field of orthopedics
• The potential applications of stem cells in treating gastrointestinal diseases
• The role of stem cells in treating metabolic disorders
• The use of stem cells in treating reproductive disorders
• The potential applications of stem cells in treating infectious diseases
• The role of stem cells in treating dental diseases
• The ethical implications of using placental stem cells
• The impact of stem cell research on the field of veterinary medicine
• The potential applications of stem cells in treating skin aging
• The role of stem cells in treating chronic pain
• The use of stem cells in treating sports injuries
• The potential applications of stem cells in treating hair loss
• The role of stem cells in enhancing athletic performance
• The ethical considerations of using stem cells in cosmetic procedures
• The impact of stem cell research on the field of agriculture
• The potential applications of stem cells in treating obesity
• The role of stem cells in treating mental health disorders
• The use of stem cells in treating addiction
• The potential applications of stem cells in enhancing cognitive function
• The role of stem cells in treating sleep disorders
• The ethical implications of using stem cells in enhancing physical appearance
• The impact of stem cell research on the field of education
• The potential applications of stem cells in enhancing creativity
• The role of stem cells in enhancing emotional intelligence
• The use of stem cells in enhancing social skills
• The potential applications of stem cells in enhancing problem-solving skills
• The role of stem cells in enhancing leadership skills
• The ethical considerations of using stem cells in enhancing intelligence
• The impact of stem cell research on the field of psychology
• The potential applications of stem cells in enhancing memory
• The role of stem cells in enhancing concentration
• The use of stem cells in enhancing motivation
• The potential applications of stem cells in enhancing productivity
• The role of stem cells in enhancing resilience
• The ethical implications of using stem cells in enhancing self-control
• The impact of stem cell research on the field of sociology
• The potential applications of stem cells in enhancing empathy
• The role of stem cells in enhancing communication skills
• The use of stem cells in enhancing conflict resolution skills
• The potential applications of stem cells in enhancing teamwork
• The role of stem cells in enhancing leadership qualities
• The ethical considerations of using stem cells in enhancing decision-making skills
• The impact of stem cell research on the field of business
• The potential applications of stem cells in enhancing negotiation skills
• The role of stem cells in enhancing time management skills
• The use of stem cells in enhancing problem-solving abilities
• The role of stem cells in enhancing critical thinking skills
• The ethical implications of using stem cells in enhancing emotional intelligence
• The ethical considerations of using stem cells in enhancing self-control
• The ethical implications of using stem cells in enhancing decision-making skills

With these stem cell essay topic ideas and examples, you are sure to find a topic that piques your interest and inspires you to write a compelling essay on this fascinating subject. Good luck!

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National Research Council (US) and Institute of Medicine (US) Committee on the Biological and Biomedical Applications of Stem Cell Research. Stem Cells and the Future of Regenerative Medicine. Washington (DC): National Academies Press (US); 2002.

Stem Cells and the Future of Regenerative Medicine.

• Hardcopy Version at National Academies Press

CHAPTER THREE Embryonic Stem Cells

E mbryonic stem cells (ESCs) are found in the inner cell mass of the human blastocyst, an early stage of the developing embryo lasting from the 4 th to 7 th day after fertilization. In normal embryonic development, they disappear after the 7 th day, and begin to form the three embryonic tissue layers. ESCs extracted from the inner cell mass during the blastocyst stage, however, can be cultured in the laboratory and under the right conditions will proliferate indefinitely. ESCs growing in this undifferentiated state retain the potential to differentiate into cells of all three embryonic tissue layers. Research involving human ESCs is at the center of the ethical debate about stem cell use and potential in regenerative medicine. Embryos from which ESCs are extracted are destroyed in the process.

Several scientific questions are important when considering the potential of stem cells for use in regenerative medicine and the policy and ethical issues that arise:

• What properties of ESCs have promise for regenerative medicine?
• What direct evidence supports ESCs' effective use in regenerative medicine?
• What obstacles and risks are associated with the use of ESCs in regenerative medicine?
• PROPERTIES OF ESCs IMPORTANT FOR REGENERATIVE MEDICINE

Human ESCs were successfully grown in the laboratory for the first time in 1998 (Thompson et al., 1998). Under appropriate culture conditions, ESCs have demonstrated a remarkable ability to self-renew continuously, that is, to produce more cells like themselves that are multipotent. As indicated at the workshop by Thomas Okarma and Ron McKay, ESC lines established from single cells have been demonstrated to proliferate through 300-400 population-doubling cycles. Human ESCs that have been propagated for more than 2 years also demonstrate a stable and normal complement of chromosomes, in contrast to the unstable and abnormal complement of embryonic cancer cell lines used in the past to study early stages of embryonic development. Careful monitoring of the aging ESC lines will be needed to evaluate the significance of genetic changes that are expected to occur over time.

Because human ESCs have only recently become available for research, most of what is known about ESCs comes from studies in the mouse, which, as noted in Chapter 2 , cannot be presumed to provide definitive evidence of the capabilities of human cells.

Nevertheless, ESCs derived from mouse blastocysts have been studied for 2 decades and provide a critical baseline of knowledge about the biology and cultivation of these cells (Torres, 1998; Wobus and Boheler, 1999). The factors that permit the mouse ESC to continue replicating in the laboratory without differentiation and methods to trigger differentiation into different cell types that exhibit normal function have been actively explored. Among the types of cells derived from cultured mouse ESCs are fat cells, various brain and nervous system cells, insulin-producing cells of the pancreas, bone cells, hematopoietic cells, yolk sac, endothelial cells, primitive endodermal cells, and smooth and striated muscle cells, including cardiomyocytes—heart muscle cells (Odorico et al., 2001).

Experience with mouse ESCs has provided clues to methods for culturing human ESCs and leading them to differentiate. Mouse ESCs will proliferate in an undifferentiated state in the presence of a biochemical called leukemia inhibitory factor (LIF), but the culture conditions required to keep human ESCs from differentiating include growing them in petri dishes on a layer of mouse embryonic fibroblasts (referred to as “feeder cells”) in a medium containing serum from cows. The feeder cells are inactivated, so they are not dividing and expanding, but they produce growth factors that sustain the ESCs. The mechanism of how feeder cells maintain the proliferation of undifferentiated ESCs is unknown. Such in vitro culturing presents certain theoretical hazards to the use of stem cells for regenerative medicine, such as the spread of viruses and other infectious agents not normally found in humans. When removed from feeder cells and grown in suspension (in liquid), human ESCs form aggregated balls of cells called “embryonic bodies,” which have been reported to give rise to a multiplicity of cell types representing all three layers of embryonic tissue development (Itskovitz-Eldor et al., 2000; Reubinoff et al., 2000; Schuldiner et al., 2000). Evidence of the differentiation in culture includes detection of the products of genes associated with different cell types and in some cases by the characteristic shapes that are peculiar to different cell types. Cells derived from human embryonic bodies include “rhythmically contracting cardiomyocytes, pigmented and nonpigmented epithelial cells, and neural cells displaying an exuberant outgrowth of axons and dendrites” (Odorico et al., 2001). In other experiments, cells arising from human ESCs have been reported to express genes associated with liver and pancreas function (Schuldiner et al., 2000). Human ESCs grown in coculture with mouse bone marrow stromal cells have been reported to produce colonies of human hematopoietic precursors and ultimately cells from the blood (Kaufman et al., 1999).

Further evidence of the multipotent capability of human ESCs is based on studies in an in vivo setting. Human ESCs injected into mice form a type of benign tumor called a teratoma that is made up of tissues from all three embryonic layers. The tissues that arise in the tumor are often advanced, organized, and complex, and include teeth, gut, hair follicles, skin, epithelium, muscle, bone, cartilage, lung tissue, and neural cells (Thompson et al., 1998). The experiments showed the capability of ESCs to produce a variety of tissues, but the results also highlight the complexity of the biological “program” of tissue development that can unfold in different biological environments. These results also emphasize the abnormal, potentially neoplastic potential of ESCs when placed into unnatural environments.

Major questions remain about the genetic or environmental factors in the body that control the fate of ESCs and about the importance of different factors during various stages of cell differentiation. Even on the basis of the limited findings, however, the ability to grow human ESCs in vitro and to have them differentiate in the laboratory makes them an important and unique tool with which to conduct the basic research that is critical for the foundation of future regenerative therapies. It has been possible, for example, to create a lineage of mouse ESCs that generate neural cell precursors (Li et al., 1998). Studies of the genes turned on and off as cells begin to differentiate, which are already under way with ESCs, will permit a better understanding of the genetic controls important in tissue differentiation (Duncan et al., 1998). In vitro studies of ESCs also provide an opportunity to explore the role of biochemicals produced in the normal cellular environment that induce stem cells to differentiate, to migrate to a site needing repair, and to assimilate into tissues (Schuldiner et al., 2000).

• EVIDENCE SUPPORTING THE POTENTIAL OF ESCS FOR USE IN REGENERATIVE MEDICINE

At the workshop, James Thomson and Thomas Okarma suggested that human ESCs will someday provide a potentially unlimited source of cells, differentiated in vitro , for transplantation therapies involving the liver, nervous system, and pancreas. Irving Weissman alluded to the possible use of ESCs to enhance the success of whole-organ transplantation. If HSCs derived from human ESCs could be successfully transplanted into the blood system of a transplant recipient (by using immunosuppressive drugs), any further implant tissue (say kidney or pancreas) developed with the same ESCs would not, in theory, be rejected by the recipient because the immune cells produced in the recipient's blood by the HSCs would see the implant tissue as “self”.

But that is a long way off, as Marcus Grompe noted, in as much as no one has yet demonstrated any in vivo reconstitution of an organ's function in either humans or experimental animals with cells derived from human ESCs. Moreover, ESCs in tissue culture give rise to a mixture of cell types all at once, and biochemical, tissue-culture, and molecular-biology techniques to control and limit differentiation require much further investigation.

Because human ESCs have only recently become available for research, and because public funding for such research has been limited, studies of how well ESCs or their differentiated tissues perform physiologic functions has been largely conducted with mouse models. Ron McKay described progress made in coaxing the in vitro differentiation of human ESCs into insulin-producing cells that might be useful in treating diabetes, but he also noted that studies have already been conducted with analogous mouse cells transplanted into mice that have diabetes and that partial restoration of insulin regulation was observed (Lumelsky et al., 2001). Other studies have demonstrated that mouse ESCs can be successfully transplanted into rodents that have Parkinson's disease symptoms and partially relieve these symptoms (Studer et al., 1998). Similarly, studies suggest that mouse ESCs can be transplanted into animals that have spinal-cord injuries and partially restore neural function (McDonald et al., 1999).

Those studies provide promise, but not definitive evidence, that similar treatments could be effective in humans. Human ESCs will need to be tested in primate models, such as those for Parkinson's disease and diabetes mellitus in the rhesus monkey. Methods for transplanting ESCs need to be developed, as do means of establishing whether the cells develop and function properly after transplantation. In some cases, it will be important to ensure that the transplanted cells or tissues are incorporated and positioned properly relative to existing tissues, such as in heart and neural tissue; the three-dimensional, cell-to-cell interactions will play important roles in the functioning of an organ. Other cells, like pancreatic islet cells, or hematopoietic cells, will require less complex incorporation.

Also, the large-scale propagation of human ESCs in culture will require that they can be grown without feeder cells (Odorico et al., 2001). Research is needed to elucidate the mechanisms of feeder cells in repressing differentiation and to find alternatives to them, at the same time eliminating the potential that an animal virus from the feeder cells might be transferred to the ESCs.

Finally, it was noted earlier that the chromosomes of human ESCs have been shown to be stable in tissue culture. This does not mean however, that ESC lines will not be subject to the random mutations that affect all cell lines as they age. In cells from humans and other animals, approximately one mutation occurs every time a cell divides. A cell that has divided 200 times in culture therefore can be expected to harbor approximately 200 different mutations (Kunkel and Bebeneck, 2000). So far, there have been no studies published about the changes that may have occurred in existing stem cell lines. Vigilant monitoring of the integrity of existing cell lines is essential to allow understanding of the impact of long-term culture, and new stem cell lines may need to be developed in the future.

Obstacles and Risks Associated with the Use of ESCs

In addition to demonstrating the functional effectiveness of ESC transplants, it is necessary to identify and minimize, or eliminate, the risks that ESCs might pose. Two identifiable risks are tumor formation and immune rejection. As noted earlier, human ESCs injected into mice can produce a benign tumor made up of diverse tissues; this response is believed to be related to the multipotency of the undifferentiated cells in an in vivo environment. However, in a small number of short-term studies in mice, human ESCs that have been allowed to begin the process of differentiation before transplantation have not resulted in significant tumor formation (Odorico et al., 2001). Obviously, this is a critical problem to understand and control.

It is too early to tell, therefore, whether it will be appropriate to use human ESCs directly in regenerative medicine. A great deal obviously must be elucidated about how the body controls the differentiation of stem cells, and this has yet to be reliably reproduced in vitro. Also, the behavior of ESCs implanted in a specific organ has not been well studied. It might someday be possible to add growth factors with a transplant to stimulate the production of a particular cell type or multiple cell types. “Inducer tissues” that interact with stem cells might be cotransplanted with ESCs to achieve a similar result. Those possibilities are still in experimental investigation.

In another respect, the possible problems associated with ESC transplantation are common to all transplantation, such as the risk of infection and the risk of tissue rejection. As discussed in Chapter 2 , rejection is a serious obstacle to successful transplantation of stem cells and tissues derived from them. It has been suggested that ESCs provoke less of an immune reaction than a whole-organ transplant, but it is unclear whether that will be true of the regenerated tissues derived from ESCs. Some types of cells (such as dendritic cells, immune system cells, and vascular endothelial cells) carry more of the histocompatibility antigens that provoke immune reactions than other cells. Those types are present in the tissues of whole organs; they connect an organ with the bloodstream and nervous system. However, tissue derived in vitro from ESCs, such as liver tissue, would not contain such cells and therefore would theoretically trigger a milder immune response; this assumes that techniques for controlling differentiation of ESCs will be available. In addition, the liver cells likely would not be devoid of all surface antigens, and so, in the absence of other techniques to reduce transplant rejection, the use of immunosuppressive drugs will still have to be used, with attendant risks of infection and toxicity.

Although difficult to conceive, the creation of a very large number of ESC lines might be one way to obtain a diversity of cells that could theoretically increase the chances of matching the histocompatibility antigens of a transplant recipient. It has also been suggested that ESCs could be made less reactive by using genetic engineering to eliminate or introduce the presence of surface antigens on them (Odorico, 2001). An exact genetic match between a transplant recipient and tissue generated from ESCs could also, in theory, be achieved by using somatic cell nuclear transfer to create histocompatible ESCs ( Figure 4 ). Cells created with this technique would overcome the problem of immune rejection. However, it might to not be appropriate to transplant such cells in a person with a genetically based disease, since the cells would carry the same genetic information. In any case, an understanding of how to prevent rejection of transplanted cells is fundamental to their becoming useful for regenerative medicine and represents one of the greatest challenges for research in this field.

Somatic Cell Nuclear Transfer (SCNT)

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Home — Essay Samples — Nursing & Health — Stem Cell Research — Stem Cell Research: The Importance and Future Potential

Stem Cell Research: The Importance and Future Potential

• Categories: Stem Cell Research

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Words: 880 |

Published: Jan 30, 2024

Words: 880 | Pages: 2 | 5 min read

Table of contents

Introduction, body paragraph 1, body paragraph 2, body paragraph 3, body paragraph 4, body paragraph 5.

• Journal of Clinical Investigation, "Transplantation of allogeneic stem cells improves survival of adults with acute lymphoblastic leukemia'"
• Journal of Neuroscience Research, "Transplantation of stem cells from human exfoliated deciduous teeth for bone repair: a preclinical study in a rat model"
• National Institutes of Health, "Induced Pluripotent Stem Cells"

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Stem cells: what they are and what they do.

Stem cells offer promise for new medical treatments. Learn about stem cell types, current and possible uses, and the state of research and practice.

You've heard about stem cells in the news, and perhaps you've wondered if they might help you or a loved one with a serious disease. Here are some answers to frequently asked questions about stem cells.

What are stem cells?

Stem cells: The body's master cells

Stem cells are the body's master cells. All other cells arise from stem cells, including blood cells, nerve cells and other cells.

Stem cells are a special type of cells that have two important properties. They are able to make more cells like themselves. That is, they self-renew. And they can become other cells that do different things in a process known as differentiation. Stem cells are found in almost all tissues of the body. And they are needed for the maintenance of tissue as well as for repair after injury.

Depending on where the stem cells are, they can develop into different tissues. For example, hematopoietic stem cells reside in the bone marrow and can produce all the cells that function in the blood. Stem cells also can become brain cells, heart muscle cells, bone cells or other cell types.

There are various types of stem cells. Embryonic stem cells are the most versatile since they can develop into all the cells of the developing fetus. The majority of stem cells in the body have fewer abilities to give rise to cells and may only help maintain and repair the tissues and organs in which they reside.

No other cell in the body has the natural ability to generate new cell types.

Why is there such an interest in stem cells?

Researchers are studying stem cells to see if they can help to:

• Increase understanding of how diseases occur. By watching stem cells mature into cells in bones, heart muscle, nerves, and other organs and tissue, researchers may better understand how diseases and conditions develop.

Generate healthy cells to replace cells affected by disease (regenerative medicine). Stem cells can be guided into becoming specific cells that can be used in people to regenerate and repair tissues that have been damaged or affected by disease.

People who might benefit from stem cell therapies include those with leukemia, Hodgkin disease, non-Hodgkin lymphoma and some solid tumor cancers. Stem cell therapies also might benefit people who have aplastic anemia, immunodeficiencies and inherited conditions of metabolism.

Stem cells are being studied to treat type 1 diabetes, Parkinson's disease, amyotrophic lateral sclerosis, heart failure, osteoarthritis and other conditions.

Stem cells may have the potential to be grown to become new tissue for use in transplant and regenerative medicine. Researchers continue to advance the knowledge on stem cells and their applications in transplant and regenerative medicine.

Test new drugs for safety and effectiveness. Before giving drugs in development to people, researchers can use some types of stem cells to test the drugs for safety and quality. This type of testing may help assess drugs in development for toxicity to the heart.

New areas of study include the effectiveness of using human stem cells that have been programmed into tissue-specific cells to test new drugs. For the testing of new drugs to be accurate, the cells must be programmed to acquire properties of the type of cells targeted by the drug. Techniques to program cells into specific cells are under study.

Where do stem cells come from?

There are several sources of stem cells:

Embryonic stem cells. These stem cells come from embryos that are 3 to 5 days old. At this stage, an embryo is called a blastocyst and has about 150 cells.

These are pluripotent (ploo-RIP-uh-tunt) stem cells, meaning they can divide into more stem cells or can become any type of cell in the body. This allows embryonic stem cells to be used to regenerate or repair diseased tissue and organs.

• Adult stem cells. These stem cells are found in small numbers in most adult tissues, such as bone marrow or fat. Compared with embryonic stem cells, adult stem cells have a more limited ability to give rise to various cells of the body.

Adult cells altered to have properties of embryonic stem cells. Scientists have transformed regular adult cells into stem cells using genetic reprogramming. By altering the genes in the adult cells, researchers can make the cells act similarly to embryonic stem cells. These cells are called induced pluripotent stem cells (iPSCs).

This new technique may allow use of reprogrammed cells instead of embryonic stem cells and prevent immune system rejection of the new stem cells. However, scientists don't yet know whether using altered adult cells will cause adverse effects in humans.

Researchers have been able to take regular connective tissue cells and reprogram them to become functional heart cells. In studies, animals with heart failure that were injected with new heart cells had better heart function and survival time.

Perinatal stem cells. Researchers have discovered stem cells in amniotic fluid as well as umbilical cord blood. These stem cells can change into specialized cells.

Amniotic fluid fills the sac that surrounds and protects a developing fetus in the uterus. Researchers have identified stem cells in samples of amniotic fluid drawn from pregnant women for testing or treatment — a procedure called amniocentesis.

Why is there controversy about using embryonic stem cells?

The National Institutes of Health created guidelines for human stem cell research in 2009. The guidelines define embryonic stem cells and how they may be used in research and include recommendations for the donation of embryonic stem cells. Also, the guidelines state that embryonic stem cells from embryos created by in vitro fertilization can be used only when the embryo is no longer needed.

Where do these embryos come from?

The embryos being used in embryonic stem cell research come from eggs that were fertilized at in vitro fertilization clinics but never implanted in women's uteruses. The stem cells are donated with informed consent from donors. The stem cells can live and grow in special solutions in test tubes or petri dishes in laboratories.

Why can't researchers use adult stem cells instead?

Progress in cell reprogramming and the formation of iPSCs has greatly enhanced research in this field. However, reprogramming is an inefficient process. When possible, iPSCs are used instead of embryonic stem cells since this avoids the ethical issues about use of embryonic stem cells that may be morally objectionable for some people.

Although research into adult stem cells is promising, adult stem cells may not be as versatile and durable as are embryonic stem cells. Adult stem cells may not be able to be manipulated to produce all cell types, which limits how adult stem cells can be used to treat diseases.

Adult stem cells are also more likely to contain irregularities due to environmental hazards, such as toxins, or from errors acquired by the cells during replication. However, researchers have found that adult stem cells are more adaptable than was first thought.

What are stem cell lines, and why do researchers want to use them?

A stem cell line is a group of cells that all descend from a single original stem cell and are grown in a lab. Cells in a stem cell line keep growing but don't become specialized cells. Ideally, they remain free of genetic defects and continue to create more stem cells. Clusters of cells can be taken from a stem cell line and frozen for storage or shared with other researchers.

What is stem cell therapy (regenerative medicine), and how does it work?

Stem cell therapy, also known as regenerative medicine, promotes the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. It is the next chapter in organ transplantation and uses cells instead of donor organs, which are limited in supply.

Researchers grow stem cells in a lab. These stem cells are manipulated to specialize into specific types of cells, such as heart muscle cells, blood cells or nerve cells.

The specialized cells can then be implanted into a person. For example, if the person has heart disease, the cells could be injected into the heart muscle. The healthy transplanted heart muscle cells could then contribute to repairing the injured heart muscle.

Researchers have already shown that adult bone marrow cells guided to become heart-like cells can repair heart tissue in people, and more research is ongoing.

Have stem cells already been used to treat diseases?

Yes. Doctors have performed stem cell transplants, also known as bone marrow transplants, for many decades. In hematopoietic stem cell transplants, stem cells replace cells damaged by chemotherapy or disease or serve as a way for the donor's immune system to fight some types of cancer and blood-related diseases. Leukemia, lymphoma, neuroblastoma and multiple myeloma often are treated this way. These transplants use adult stem cells or umbilical cord blood.

Researchers are testing adult stem cells to treat other conditions, including some degenerative diseases such as heart failure.

What are the potential problems with using embryonic stem cells in humans?

For embryonic stem cells to be useful, researchers must be certain that the stem cells will differentiate into the specific cell types desired.

Researchers have discovered ways to direct stem cells to become specific types of cells, such as directing embryonic stem cells to become heart cells. Research is ongoing in this area.

Embryonic stem cells also can grow irregularly or specialize in different cell types spontaneously. Researchers are studying how to control the growth and development of embryonic stem cells.

Embryonic stem cells also might trigger an immune response in which the recipient's body attacks the stem cells as foreign invaders, or the stem cells might simply fail to function as expected, with unknown consequences. Researchers continue to study how to avoid these possible complications.

What is therapeutic cloning, and what benefits might it offer?

Therapeutic cloning, also called somatic cell nuclear transfer, is a way to create versatile stem cells independent of fertilized eggs. In this technique, the nucleus is removed from an unfertilized egg. This nucleus contains the genetic material. The nucleus also is removed from the cell of a donor.

This donor nucleus is then injected into the egg, replacing the nucleus that was removed, in a process called nuclear transfer. The egg is allowed to divide and soon forms a blastocyst. This process creates a line of stem cells that is genetically identical to the donor's cells — in essence, a clone.

Some researchers believe that stem cells derived from therapeutic cloning may offer benefits over those from fertilized eggs because cloned cells are less likely to be rejected once transplanted back into the donor. And it may allow researchers to see exactly how a disease develops.

Has therapeutic cloning in people been successful?

No. Researchers haven't been able to successfully perform therapeutic cloning with humans despite success in a number of other species.

Researchers continue to study the potential of therapeutic cloning in people.

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• Stem cell basics. National Institutes of Health. https://stemcells.nih.gov/info/basics/stc-basics/#stc-I. Accessed March 21, 2024.
• Lovell-Badge R, et al. ISSCR guidelines for stem cell research and clinical translation: The 2021 update. Stem Cell Reports. 2021; doi:10.1016/j.stemcr.2021.05.012.
• AskMayoExpert. Hematopoietic stem cell transplant. Mayo Clinic; 2024.
• Stem cell transplants in cancer treatment. National Cancer Institute. https://www.cancer.gov/about-cancer/treatment/types/stem-cell-transplant/. Accessed March 21, 2024.
• Townsend CM Jr, et al. Regenerative medicine. In: Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice. 21st ed. Elsevier; 2022. https://www.clinicalkey.com. Accessed March 21, 2024.
• Kumar D, et al. Stem cell based preclinical drug development and toxicity prediction. Current Pharmaceutical Design. 2021; doi:10.2174/1381612826666201019104712.
• NIH guidelines for human stem cell research. National Institutes of Health. https://stemcells.nih.gov/research-policy/guidelines-for-human-stem-cell-research. Accessed March 21, 2024.
• De la Torre P, et al. Current status and future prospects of perinatal stem cells. Genes. 2020; doi:10.3390/genes12010006.
• Yen Ling Wang A. Human induced pluripotent stem cell-derived exosomes as a new therapeutic strategy for various diseases. International Journal of Molecular Sciences. 2021; doi:10.3390/ijms22041769.
• Alessandrini M, et al. Stem cell therapy for neurological disorders. South African Medical Journal. 2019; doi:10.7196/SAMJ.2019.v109i8b.14009.
• Goldenberg D, et al. Regenerative engineering: Current applications and future perspectives. Frontiers in Surgery. 2021; doi:10.3389/fsurg.2021.731031.
• Brown MA, et al. Update on stem cell technologies in congenital heart disease. Journal of Cardiac Surgery. 2020; doi:10.1111/jocs.14312.
• Li M, et al. Brachyury engineers cardiac repair competent stem cells. Stem Cells Translational Medicine. 2021; doi:10.1002/sctm.20-0193.
• Augustine R, et al. Stem cell-based approaches in cardiac tissue engineering: Controlling the microenvironment for autologous cells. Biomedical Pharmacotherapy. 2021; doi:10.1016/j.biopha.2021.111425.
• Cloning fact sheet. National Human Genome Research Institute. https://www.genome.gov/about-genomics/fact-sheets/Cloning-Fact-Sheet. Accessed March 21, 2024.
• Dingli D (expert opinion). Mayo Clinic. Nov. 17, 2023.

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Examining the ethics of embryonic stem cell research

Following the recent passage by both houses of Congress of the Stem Cell Research Enhancement Act of 2007, which would permit federal funding of research using donated surplus embryonic stem cells from fertility clinics, the president has once again threatened a veto.

Because neither the House nor the Senate had sufficient votes to override a presidential veto, it appears unlikely this new bill will be enacted into law, further stalling the pace of this research. “This bill crosses a moral line that I and others find troubling,” stated Bush, following the Senate’s vote.

SCL : What are th e main arguments for and against embryonic stem cell research? MS : Proponents argue that embryonic stem cell research holds great promise for understanding and curing diabetes, Parkinson’s disease, spinal cord injury, and other debilitating conditions. Opponents argue that the research is unethical, because deriving the stem cells destroys the blastocyst, an unimplanted human embryo at the sixth to eighth day of development. As Bush declared when he vetoed last year’s stem cell bill, the federal government should not support “the taking of innocent human life.”

It is surprising that, despite the extensive public debate—in Congress, during the 2004 and 2006 election campaigns, and on the Sunday morning talk shows—relatively little attention has been paid to the moral issue at the heart of the controversy: Are the opponents of stem cell research correct in their claim that the unimplanted human embryo is already a human being, morally equivalent to a person?

“It is important to be clear about the embryo from which stem cells are extracted. It is not implanted and growing in a woman’s uterus. It is not a fetus. It has no recognizable human features or form. It is, rather, a blastocyst, a cluster of 180 to 200 cells, growing in a petri dish, barely visible to the naked eye.”

SCL : What are the contradictions in Bush’s stance? MS : Before we address that, it is important to be clear about the embryo from which stem cells are extracted. It is not implanted and growing in a woman’s uterus. It is not a fetus. It has no recognizable human features or form.

It is, rather, a blastocyst, a cluster of 180 to 200 cells, growing in a petri dish, barely visible to the naked eye. Such blastocysts are either cloned in the lab or created in fertility clinics. The bill recently passed by Congress would fund stem cell research only on excess blastocysts left over from infertility treatments.

The blastocyst represents such an early stage of embryonic development that the cells it contains have not yet differentiated, or taken on the properties of particular organs or tissues—kidneys, muscles, spinal cord, and so on. This is why the stem cells that are extracted from the blastocyst hold the promise of developing, with proper coaxing in the lab, into any kind of cell the researcher wants to study or repair.

The moral and political controversy arises from the fact that extracting the stem cells destroys the blastocyst. It is important to grasp the full force of the claim that the embryo is morally equivalent to a person, a fully developed human being.

For those who hold this view, extracting stem cells from a blastocyst is as morally abhorrent as harvesting organs from a baby to save other people’s lives. This is the position of Senator Sam Brownback, Republican of Kansas, a leading advocate of the right-to-life position. In Brownback’s view, “a human embryo . . . is a human being just like you and me; and it deserves the same respect that our laws give to us all.

If Brownback is right, then embryonic stem cell research is immoral because it amounts to killing a person to treat other people’s diseases.

SCL : What is the basis for the belief that personhood begins at conception? MS : Some base this belief on the religious conviction that the soul enters the body at the moment of conception. Others defend it without recourse to religion, by the following line of reasoning: Human beings are not things. Their lives must not be sacrificed against their will, even for the sake of good ends, like saving other people’s lives. The reason human beings must not be treated as things is that they are inviolable. At what point do humans acquire this inviolability? The answer cannot depend on the age or developmental stage of a particular human life. Infants are inviolable, and few people would countenance harvesting organs for transplantation even from a fetus.

Every human being—each one of us—began life as an embryo. Unless we can point to a definitive moment in the passage from conception to birth that marks the emergence of the human person, we must regard embryos as possessing the same inviolability as fully developed human beings.

SCL : By this line of reasoning, human embryos are inviolable and should not be used for research, even if that research might save many lives. MS : Yes, but this argument can be challenged on a number of grounds. First, it is undeniable that a human embryo is “human life” in the biological sense that it is living rather than dead, and human rather than, say, bovine.

But this biological fact does not establish that the blastocyst is a human being, or a person. Any living human cell (a skin cell, for example) is “human life” in the sense of being human rather than bovine and living rather than dead. But no one would consider a skin cell a person, or deem it inviolable. Showing that a blastocyst is a human being, or a person, requires further argument.

Some try to base such an argument on the fact that human beings develop from embryo to fetus to child. Every person was once an embryo, the argument goes, and there is no clear, non-arbitrary line between conception and adulthood that can tell us when personhood begins. Given the lack of such a line, we should regard the blastocyst as a person, as morally equivalent to a fully developed human being.

SCL : What is the flaw in this argument? MS : Consider an analogy: although every oak tree was once an acorn, it does not follow that acorns are oak trees, or that I should treat the loss of an acorn eaten by a squirrel in my front yard as the same kind of loss as the death of an oak tree felled by a storm. Despite their developmental continuity, acorns and oak trees differ. So do human embryos and human beings, and in the same way. Just as acorns are potential oaks, human embryos are potential human beings.

The distinction between a potential person and an actual one makes a moral difference. Sentient creatures make claims on us that nonsentient ones do not; beings capable of experience and consciousness make higher claims still. Human life develops by degrees.

SCL : Yet there are people who disagree that life develops by degrees, and believe that a blastocyst is a person and, therefore, morally equivalent to a fully developed human being. MS : Certainly some people hold this belief. But a reason to be skeptical of the notion that blastocysts are persons is to notice that many who invoke it do not embrace its full implications.

President Bush is a case in point. In 2001, he announced a policy that restricted federal funding to already existing stem cell lines, so that no taxpayer funds would encourage or support the destruction of embryos. And in 2006, he vetoed a bill that would have funded new embryonic stem cell research, saying that he did not want to support “the taking of innocent human life.”

“The distinction between a potential person and an actual one makes a moral difference. Sentient creatures make claims on us that nonsentient ones do not; beings capable of experience and consciousness make higher claims still. Human life develops by degrees.”

But it is a striking feature of the president’s position that, while restricting the funding of embryonic stem cell research, he has made no effort to ban it. To adapt a slogan from the Clinton administration, the Bush policy might be summarized as “don’t fund, don’t ban.” But this policy is at odds with the notion that embryos are human beings.

SCL : If Bush’s policy were consistent with his stated beliefs, how, in your opinion, would it differ from his current “don’t fund, don’t ban” policy? MS : If harvesting stem cells from a blastocyst were truly on a par with harvesting organs from a baby, then the morally responsible policy would be to ban it, not merely deny it federal funding.

If some doctors made a practice of killing children to get organs for transplantation, no one would take the position that the infanticide should be ineligible for federal funding but allowed to continue in the private sector. In fact, if we were persuaded that embryonic stem cell research were tantamount to infanticide, we would not only ban it but treat it as a grisly form of murder and subject scientists who performed it to criminal punishment.

SCL : Couldn’t it be argued, in defense of the president’s policy, that Congress would be unlikely to enact an outright ban on embryonic stem cell research? MS : Perhaps. But this does not explain why, if the president really considers embryos to be human beings, he has not at least called for such a ban, nor even called upon scientists to stop doing stem cell research that involves the destruction of embryos. In fact, Bush has cited the fact that “there is no ban on embryonic stem cell research” in touting the virtues of his “balanced approach.”

The moral oddness of the Bush “don’t fund, don’t ban” position confused even his spokesman, Tony Snow. Last year, Snow told the White House press corps that the president vetoed the stem cell bill because he considered embryonic stem cell research to be “murder,” something the federal government should not support. When the comment drew a flurry of critical press attention, the White House retreated. No, the president did not believe that destroying an embryo was murder. The press secretary retracted his statement, and apologized for having “overstated the president’s position.”

How exactly the spokesman had overstated the president’s position is unclear. If embryonic stem cell research does constitute the deliberate taking of innocent human life, it is hard to see how it differs from murder. The chastened press secretary made no attempt to parse the distinction. His errant statement that the president considered embryo destruction to be “murder” simply followed the moral logic of the notion that embryos are human beings. It was a gaffe only because the Bush policy does not follow that logic.

SCL : You have stated that the president’s refusal to ban privately funded embryonic stem cell research is not the only way in which his policies betray the principle that embryos are persons. How so? MS : In the course of treating infertility, American fertility clinics routinely discard thousands of human embryos. The bill that recently passed in the Senate would fund stem cell research only on these excess embryos, which are already bound for destruction. (This is also the position taken by former governor Mitt Romney, who supports stem cell research on embryos left over from fertility clinics.) Although Bush would ban the use of such embryos in federally funded research, he has not called for legislation to ban the creation and destruction of embryos by fertility clinics.

SCL : If embryos are morally equivalent to fully developed human beings, doesn’t it then follow that allowing fertility clinics to discard thousands of embryos is condoning mass murder? MS : It does. If embryos are human beings, to allow fertility clinics to discard them is to countenance, in effect, the widespread creation and destruction of surplus children. Those who believe that a blastocyst is morally equivalent to a baby must believe that the 400,000 excess embryos languishing in freezers in U.S. fertility clinics are like newborns left to die by exposure on a mountainside. But those who view embryos in this way should not only be opposing embryonic stem cell research; they should also be leading a campaign to shut down what they must regard as rampant infanticide in fertility clinics.

Some principled right-to-life opponents of stem cell research meet this test of moral consistency. Bush’s “don’t fund, don’t ban” policy does not. Those who fail to take seriously the belief that embryos are persons miss this point. Rather than simply complain that the president’s stem cell policy allows religion to trump science, critics should ask why the president does not pursue the full implications of the principle he invokes.

If he does not want to ban embryonic stem cell research, or prosecute stem cell scientists for murder, or ban fertility clinics from creating and discarding excess embryos, this must mean that he does not really consider human embryos as morally equivalent to fully developed human beings after all.

But if he doesn’t believe that embryos are persons, then why ban federally funded embryonic stem cell research that holds promise for curing diseases and saving lives? 

75 Stem Cell Essay Topic Ideas & Examples

🏆 best stem cell topic ideas & essay examples, ⭐ good research topics about stem cell, 👍 simple & easy stem cell essay titles.

• Ethical Aspects of Stem Cell Research Firstly, the leading argument against the use of stem cell-based therapy is the fact that it leads to the destruction of a human embryo.
• Stem Cells Applications in Bone and Tooth Repair and Regeneration It provides examples of scientific research about the application of stem cells in the process of the regeneration of bones and teeth.
• Ethical and Safety Issues of Stem Cell-Based Therapy Ilic and Ogilvie argue that this is a dilemma between the obligation of doctors and scientists to save lives and the need to destroy it in order to obtain stem cells.
• Blood Stem Cell Self-Renewal and Differentiation One of the distinct cells in the blood or hematopoietic stem cell. Due to this functionality, the blood and skin cells’ pose the greatest ability of differentiation and self-renewal.
• Embryonic Stem Cells and Nuclear Transfer Somatic cell dedifferentiation is the “direct reprogramming of an adult somatic cell to return to the state of a pluripotent stem cell” The pros of nuclear transfer are that these embryonic stem cells, which contain […]
• Stem Cell Regenerative Therapy This method is well-studied and has a proven track record of improving spinal stenosis, unlike stem cells. This evidence suggests that stem cells can potentially reverse the degeneration of bone and tissue.
• “What’s the Fuss about Stem Cells?” The primary goal of this essay is to emphasize the importance of the research of the stem cells, provide a precise definition, and explain their functions in the body.
• The Stem Cell Research: Key Aspects In light of the legal aspects of the research, the paper indicates that the human embryo deserves respect just as adults.
• Apple Stem Cell in Skincare Researchers have shown that extracts from Swiss apple, Malus domestica, have regenerative effect on skin, and thus have utilized them in the production of apple stem cells from adult cells.
• Stem Cell Research: Some Pros and Cons The science of stem cell treatments, potentially as or more significant than these other innovations, is beginning a new stage of exploration and growth that could be the forerunner of unprecedented cures and therapies.
• Stem Cells Biology: Features and Researchs Stem cells are cells that have the capacity to subdivide into other cells. The second property of stem cells is that they can develop into specialized cells in the differentiation process.
• Nanoscale Silver and Stem Cell Research Whether nanoscale silver or stem cell research, patients realize that the benefits of this technology go without saying. While silver provides many effective applications, stem cell research is the best alternative for curing pancreatic cancer.
• Stem Cell Research from Catholic Perspective The argument exists that because some embryos are created in petri dishes and require implantation into a womb to achieve their full potential that they should not be considered human life, and therefore, can be […]
• Ethics of Stem Cell Research Creating Superhumans Stem cell research is a subject that has generally been absent from the current public and political debates, pushed to the backburner by issues such as the economy, the Iraq War, healthcare, and immigration.
• Stem Cell Treatment, Its Benefits and Efficiency Stem cell treatment is a method that uses the transplantation of cells to facilitate the process of cell regeneration. In conclusion, stem cell therapy is expected to provide a breakthrough in the treatment of adverse […]
• Factors That Influence Stem Cell Research For instance, the GDP of the United States measures the value of goods and services produced within the boundaries of the United States, by people living in the U.S.even if they are not American citizens. […]
• Using Embryonic Stem Cells to Grow Body Parts The use of embryonic stem cells is one of the important medical innovations of the 21st century. The process entails disassembling the embryo to get stem cells that are located in the internal parts of […]
• Kant’s Moral Philosophy on Stem Cell Research In Kant’s own words, “Autonomy of the will is the property that the will has of being a law to itself.[Morality] is the relation of actions to the autonomy of the will […].
• The Research and Use of Stem Cell Embryos Policies of governments across the globe vary on the legality of the prohibited and allowed research and use of stem cell embryos.
• Neural Stem Cells, Viral Vectors in Gene Therapy and Restriction Enzymes The nervous system is comprised of specialized type of cells called Neural Stem Cells. Developmental versatility of plasticity of neural stem cells is important in formation of these different neural cells.
• Stem Cell Research Implementation Nevertheless, the lack of adequate funding from the government has deteriorated the efforts of the researchers in embracing the benefits of this technology.
• Stem Cell Research D, in the article I am Pro-Life and Oppose Embryonic Stem Cell Research, opposes stem cell research in particular embryonic stem cell research.
• Expanding Federal Government Funding of Stem Cell Research This is because stem cell research promises to cure degenerative diseases such as Alzheimer’s and scoliosis but the same time the cure requires the destruction of human embryonic stem cells that can only be had […]
• Adipose-Derived Mesenchymal Stem Cell Application Combined With Fibrin Matrix
• Embryonic Stem Cell Research Provides Revolutionary and Life-Saving Breakthroughs
• Immune Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation
• Ethical and Beneficial Replacement for Embryonic Stem Cell Research
• Biopsy Needle Advancement During Bone Marrow Aspiration and Mesenchymal Stem Cell Concentration
• Autoimmunity Following Allogeneic Hematopoietic Stem Cell Transplantation
• Bioinformatics Analysis and Biomarkers With Cancer Stem Cell Characteristics in Lung Squamous Cell Carcinoma
• Induced Pluripotent Stem Cell-Based Cancer Vaccines
• Embryonic Stem Cell Research: A New Paradigm in Medical Technology
• Advanced Functional Biomaterials for Stem Cell Delivery in Regenerative Engineering and Medicine
• Pragmatic Pluralism: Mutual Tolerance of Contested Understandings Between Orthodox and Alternative Practitioners in Autologous Stem Cell Transplantation
• Allogeneic Hematopoietic Stem Cell Transplantation in a Rare Case of Tonsillar Mast Cell Sarcoma
• Stem Cell Fate Determination During Development and Regeneration of Ectodermal Organs
• Biomimetic Extracellular Matrix Mediated Somatic Stem Cell Differentiation: Applications in Dental Pulp Tissue Regeneration
• Adult Stem Cell and Mesenchymal Progenitor Theories of Aging
• Ethical, Legal, and Social Issues in Genome or Stem Cell Research
• Defective Pulmonary Innate Immune Responses Post-stem Cell Transplantation
• Stem Cell Therapy for Diabetes
• Embryonic Stem Cell Research: The Pandora’s Box of Science
• Bone Marrow Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
• Human Organ Culture: Updating the Approach to Bridge the Gap From in Vitro to in Vivo in Inflammation, Cancer, and Stem Cell Biology
• Adult Stem Cell Therapies for Wound Healing: Biomaterials and Computational Models
• Evaluating the Endocytosis and Lineage-Specification Properties of Mesenchymal Stem Cell-Derived Extracellular Vesicles for Targeted Therapeutic Applications
• Hematopoietic Stem Cell Transcription Factors in Cardiovascular Pathology
• Central Nervous System Complications in Children Receiving Chemotherapy or Hematopoietic Stem Cell Transplantation
• Christian Ethics and Embryonic Stem Cell Research
• Funding Stem Cell Research: A New Field of Innovative Medicine
• Mesenchymal Stem Cell-Derived Extracellular Vesicles in Aging
• Stem Cell Research and Its Effects on the Future of Medicine
• Developing Stem Cell-Based Therapies for Neural Repair
• Bioethical and Political Debates Surrounding Embryonic Stem Cell Research
• Autologous Hematopoietic Stem Cell Transplantation for Treatment of Systemic Sclerosis
• Mitochondrial Medicine: Genetic Underpinnings and Disease Modeling Using Induced Pluripotent Stem Cell Technology
• Dental Mesenchymal Stem Cell-Based Translational Regenerative Dentistry: From Artificial to Biological Replacement
• Embryonic Stem Cell Research Could Help Out Many People
• Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via Akt Activation
• Human Liver Stem Cell-Derived Extracellular Vesicles Prevent Aristolochic Acid-Induced Kidney Fibrosis
• Stem Cell Therapy for Pediatric Traumatic Brain Injury
• Continuous Immune Cell Differentiation Inferred From Single-Cell Measurements Following Allogeneic Stem Cell Transplantation
• Stem Cell-Friendly Scaffold Biomaterials: Applications for Bone Tissue Engineering and Regenerative Medicine
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Stem-cell research articles from across Nature Portfolio

Stem-cell research is the area of research that studies the properties of stem cells and their potential use in medicine. As stem cells are the source of all tissues, understanding their properties helps in our understanding of the healthy and diseased body's development and homeostasis.

Latest Research and Reviews

Long-term lineage commitment in hematopoietic stem cell gene therapy.

• Andrea Calabria
• Giulio Spinozzi
• Eugenio Montini

YTHDC1-mediated microRNA maturation is essential for hematopoietic stem cells maintenance

Skeletal stem and progenitor cells in bone physiology, ageing and disease

Various populations of skeletal stem and progenitor cells (SSPCs) exist within the native skeletal environments of humans and mice, with complex roles in the maintenance of bone tissue. This Review discusses the current state of knowledge of the identity and roles of SSPCs in skeletal health, disease and ageing.

• Seppe Melis
• Dana Trompet
• Christa Maes

Bio-printing method as a novel approach to obtain a fibrin scaffold settled by limbal epithelial cells for corneal regeneration

• Krzysztof Pietryga
• Katarzyna Jesse
• Edward Wylęgała

Anti-inflammatory Prowess of endothelial progenitor cells in the realm of biology and medicine

• Mehdi Hassanpour
• Amankeldi A. Salybkov
• Takayuki Asahara

p21 Regulates Wnt-Notch balance via DREAM/MMB/Rb-E2F1 and maintains intestinal stem cell homeostasis

• Liangxia Jiang

News and Comment

Comparison of allo-SCT versus consolidation chemotherapy as post-remission therapy in acute lymphoblastic leukaemia aged ≥55 years

• Yu-Qian Sun

(Donor) age is more than just a number…

• Amelia A. Langston

Impact of JACIE accreditation on safety of patient care: healthcare providers perspective from a tertiary care stem cell transplant center in Saudi Arabia

• Mohamed Bayoumy
• Ahlam Almasari
• Wasil Jastaniah

Wine without alcohol: medicine without doctors!

• Shaun R. McCann

Durable remission of refractory and advanced stage mycosis fungoides/sezary syndrome utilizing an “outpatient” alemtuzumab, fludarabine-based reduced intensity allogeneic hematopoietic cell transplantation

• Ramaprasad Srinivasan
• Richard Childs

Real-world outcomes of tandem ASCT in newly diagnosed multiple myeloma patients with standard risk features: a single-center analysis

• Andrea Poveda-García
• Estela Ruiz
• Valentín Cabañas

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