Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide (through mitosis) to produce more stem cells. They are found in multicellular organisms. In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cells—ectoderm, endoderm and mesoderm (see induced pluripotent stem cells)—but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues.
There are three known accessible sources of autologous adult stem cells in humans:
- Bone marrow, which requires extraction by harvesting, that is, drilling into bone (typically the femur or iliac crest).
- Adipose tissue (lipid cells), which requires extraction by liposuction.
- Blood, which requires extraction through apheresis, wherein blood is drawn from the donor (similar to a blood donation), and passed through a machine that extracts the stem cells and returns other portions of the blood to the donor.
Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank his or her own blood for elective surgical procedures.
Adult stem cells are frequently used in various medical therapies (e.g., bone marrow transplantation). Stem cells can now be artificially grown and transformed (differentiated) into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves. Embryonic cell lines and autologous embryonic stem cells generated through somatic cell nuclear transfer or dedifferentiation have also been proposed as promising candidates for future therapies. Research into stem cells grew out of findings by Ernest A. McCulloch and James E. Till at the University of Toronto in the 1960s.
The classical definition of a stem cell requires that it possesses two properties:
- Self-renewal: the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
- Potency: the capacity to differentiate into specialized cell types. In the strictest sense, this requires stem cells to be either totipotent or pluripotent—to be able to give rise to any mature cell type, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells. Apart from this it is said that stem cell function is regulated in a feed back mechanism.
Two mechanisms exist to ensure that a stem cell population is maintained:
- Obligatory asymmetric replication: a stem cell divides into one mother cell that is identical to the original stem cell, and another daughter cell that is differentiated.
- Stochastic differentiation: when one stem cell develops into two differentiated daughter cells, another stem cell undergoes mitosis and produces two stem cells identical to the original.
Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.
- Totipotent (a.k.a. omnipotent) stem cells can differentiate into embryonic and extraembryonic cell types. Such cells can construct a complete, viable organism. These cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent.
- Pluripotent stem cells are the descendants of totipotent cells and can differentiate into nearly all cells, i.e. cells derived from any of the three germ layers.
- Multipotent stem cells can differentiate into a number of cell types, but only those of a closely related family of cells.
- Oligopotent stem cells can differentiate into only a few cell types, such as lymphoid or myeloid stem cells.
- Unipotent cells can produce only one cell type, their own, but have the property of self-renewal, which distinguishes them from non-stem cells (e.g. progenitor cells, which cannot self-renew).
In practice, stem cells are identified by whether they can regenerate tissue. For example, the defining test for bone marrow or hematopoietic stem cells (HSCs) is the ability to transplant the cells and save an individual without HSCs. This demonstrates that the cells can produce new blood cells over a long term. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.
Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, in which single cells are assessed for their ability to differentiate and self-renew. Stem cells can also be isolated by their possession of a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells shall behave in a similar manner in vivo. There is considerable debate as to whether some proposed adult cell populations are truly stem cells.
Embryonic stem (ES) cells are the cells of the inner cell mass of a blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells. ES cells are pluripotent and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta.
During embryonic development these inner cell mass cells continuously divide and become more specialized. For example, a portion of the ectoderm in the dorsal part of the embryo specializes as 'neurectoderm', which will become the future central nervous system. Later in development, neurulation causes the neurectoderm to form the neural tube. At the neural tube stage, the anterior portion undergoes encephalization to generate or 'pattern' the basic form of the brain. At this stage of development, the principal cell type of the CNS is considered a neural stem cell. These neural stem cells are pluripotent, as they can generate a large diversity of many different neuron types, each with unique gene expression, morphological, and functional characteristics. The process of generating neurons from stem cells is called neurogenesis. One prominent example of a neural stem cell is the radial glial cell, so named because it has a distinctive bipolar morphology with highly elongated processes spanning the thickness of the neural tube wall, and because historically it shared some glial characteristics, most notably the expression of glial fibrillary acidic protein (GFAP). The radial glial cell is the primary neural stem cell of the developing vertebrate CNS, and its cell body resides in the ventricular zone, adjacent to the developing ventricular system. Neural stem cells are committed to the neuronal lineages (neurons, astrocytes, and oligodendrocytes), and thus their potency is restricted.
Nearly all research to date has made use of mouse embryonic stem cells (mES) or human embryonic stem cells (hES) derived from the early inner cell mass. Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin as an extracellular matrix (for support) and require the presence of leukemia inhibitory factor (LIF) in serum media. A drug cocktail containing inhibitors to GSK3B and the MAPK/ERK pathway, called 2i, has also been shown to maintain pluripotency in stem cell culture. Human ES cells are grown on a feeder layer of mouse embryonic fibroblasts (MEFs) and require the presence of basic fibroblast growth factor (bFGF or FGF-2). Without optimal culture conditions or genetic manipulation, embryonic stem cells will rapidly differentiate.
A human embryonic stem cell is also defined by the expression of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and Sox2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency. The cell surface antigens most commonly used to identify hES cells are the glycolipids stage specific embryonic antigen 3 and 4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. By using human embryonic stem cells to produce specialized cells like nerve cells or heart cells in the lab, scientists can gain access to adult human cells without taking tissue from patients. They can then study these specialized adult cells in detail to try and catch complications of diseases, or to study cells reactions to potentially new drugs. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.
There are currently no approved treatments using embryonic stem cells. The first human trial was approved by the US Food and Drug Administration in January 2009. However, the human trial was not initiated until October 13, 2010 in Atlanta for spinal cord injury research. On November 14, 2011 the company conducting the trial (Geron Corporation) announced that it will discontinue further development of its stem cell programs. ES cells, being pluripotent cells, require specific signals for correct differentiation—if injected directly into another body, ES cells will differentiate into many different types of cells, causing a teratoma. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face. Due to ethical considerations, many nations currently have moratoria or limitations on either human ES cell research or the production of new human ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease..
The primitive stem cells located in the organs of fetuses are referred to as fetal stem cells. There are two types of fetal stem cells:
- Fetal proper stem cells come from the tissue of the fetus proper, and are generally obtained after an abortion. These stem cells are not immortal but have a high level of division and are multipotent.
- Extraembryonic fetal stem cells come from extraembryonic membranes, and are generally not distinguished from adult stem cells. These stem cells are acquired after birth, they are not immortal but have a high level of cell division, and are pluripotent.
Adult stem cells, also called somatic (from Greek σωματικóς, "of the body") stem cells, are stem cells which maintain and repair the tissue in which they are found. They can be found in children, as well as adults.
Pluripotent adult stem cells are rare and generally small in number, but they can be found in umbilical cord blood and other tissues. Bone marrow is a rich source of adult stem cells, which have been used in treating several conditions including liver cirrhosis, chronic limb ischemia  and endstage heart failure. The quantity of bone marrow stem cells declines with age and is greater in males than females during reproductive years. Much adult stem cell research to date has aimed to characterize their potency and self-renewal capabilities. DNA damage accumulates with age in both stem cells and the cells that comprise the stem cell environment. This accumulation is considered to be responsible, at least in part, for increasing stem cell dysfunction with aging (see DNA damage theory of aging).
Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, dental pulp stem cell, etc.). Muse cells (multi-lineage differentiating stress enduring cells) are a recently discovered pluripotent stem cell type found in multiple adult tissues, including adipose, dermal fibroblasts, and bone marrow. While rare, muse cells are identifiable by their expression of SSEA-3, a marker for undifferentiated stem cells, and general mesenchymal stem cells markers such as CD105. When subjected to single cell suspension culture, the cells will generate clusters that are similar to embryoid bodies in morphology as well as gene expression, including canonical pluripotency markers Oct4, Sox2, and Nanog.
Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants. Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses.
The use of adult stem cells in research and therapy is not as controversial as the use of embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Additionally, in instances where adult stem cells are obtained from the intended recipient (an autograft), the risk of rejection is essentially non-existent. Consequently, more US government funding is being provided for adult stem cell research.
Multipotent stem cells are also found in amniotic fluid. These stem cells are very active, expand extensively without feeders and are not tumorigenic. Amniotic stem cells are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines. Amniotic stem cells are a topic of active research.
Use of stem cells from amniotic fluid overcomes the ethical objections to using human embryos as a source of cells. Roman Catholic teaching forbids the use of embryonic stem cells in experimentation; accordingly, the Vatican newspaper "Osservatore Romano" called amniotic stem cells "the future of medicine".
It is possible to collect amniotic stem cells for donors or for autologuous use: the first US amniotic stem cells bank  was opened in 2009 in Medford, MA, by Biocell Center Corporation and collaborates with various hospitals and universities all over the world.
However, reprogramming allows for the creation of pluripotent cells, induced pluripotent stem cells, from adult cells. It is important to note that these are not adult stem cells, but adult cells (e.g. epithelial cells) reprogrammed to give rise to cells with pluripotent capabilities. Using genetic reprogramming with protein transcription factors, pluripotent stem cells with ESC-like capabilities have been derived. The first demonstration of Induced Pluripotent Stem Cells was conducted by Shinya Yamanaka and his colleagues at Kyoto University. They used the transcription factors Oct3/4, Sox2, c-Myc, and Klf4 to reprogram mouse fibroblast cells into pluripotent cells. Subsequent work used these factors to induce pluripotency in human fibroblast cells. Junying Yu, James Thomson, and their colleagues at the University of Wisconsin–Madison used a different set of factors, Oct4, Sox2, Nanog and Lin28, and carried out their experiments using cells from human foreskin. However, they were able to replicate Yamanaka's finding that inducing pluripotency in human cells was possible.
It is important to note that iPSCs and ESCs are not equivalent. They have many similar properties, such as pluripotency and differentiation potential, the expression of pluripotency genes, epigenetic patterns, embryoid body and teratoma formation, and viable chimera formation. However, similar does not mean they are the same. In fact, there are many differences within these properties. Importantly, the chromatin of iPSCs appears to be more "closed" or methylated than that of ESCs. Similarly, the gene expression pattern between ESCs and iPSCs, or even iPSCs sourced from different origins. There are thus questions about the "completeness" of reprogramming and the somatic memory of induced pluripotent stem cells. Despite this, inducing adult cells to be pluripotent appears to be viable.
As a result of the success of these experiments, Ian Wilmut, who helped create the first cloned animal Dolly the Sheep, has announced that he will abandon somatic cell nuclear transfer as an avenue of research.
Furthermore, induced pluripotent stem cells provide several therapeutic advantages. Like ESCs, they are pluripotent. They thus have great differentiation potential; theoretically, they could produce any cell within the human body (if reprogramming to pluripotency was "complete"). Moreover, unlike ESCs, they potentially could allow doctors to create a pluripotent stem cell line for each individual patient. In fact, frozen blood samples can be used as a source of induced pluripotent stem cells, opening a new avenue for obtaining the valued cells. Patient specific stem cells allow for the screening for side effects before drug treatment, as well as the reduced risk of transplantation rejection. Despite their current limited use therapeutically, iPSCs hold create potential for future use in medical treatment and research.
To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.
An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in Drosophila germarium have identified the signals decapentaplegic and adherens junctions that prevent germarium stem cells from differentiating.
Stem cell therapy is the use of stem cells to treat or prevent a disease or condition. Bone marrow transplant is a form of stem cell therapy that has been used for many years without controversy. No stem cell therapies other than bone marrow transplant are widely used.
Stem cell treatments may require immunosuppression because of a requirement for radiation before the transplant to remove the person's previous cells, or because the patient's immune system may target the stem cells. One approach to avoid the second possibility is to use stem cells from the same patient who is being treated.
Pluripotency in certain stem cells could also make it difficult to obtain a specific cell type. It is also difficult to obtain the exact cell type needed, because not all cells in a population differentiate uniformly. Undifferentiated cells can create tissues other than desired types.
Some stem cells form tumors after transplantation; pluripotency is linked to tumor formation especially in embryonic stem cells, fetal proper stem cells, induced pluripotent stem cells. Fetal proper stem cells form tumors despite multipotency.
Some of the fundamental patents covering human embryonic stem cells are owned by the Wisconsin Alumni Research Foundation (WARF) – they are patents 5,843,780, 6,200,806, and 7,029,913 invented by James A. Thomson. WARF does not enforce these patents against academic scientists, but does enforce them against companies.
In 2006, a request for the US Patent and Trademark Office (USPTO) to re-examine the three patents was filed by the Public Patent Foundation on behalf of its client, the non-profit patent-watchdog group Consumer Watchdog (formerly the Foundation for Taxpayer and Consumer Rights). In the re-examination process, which involves several rounds of discussion between the USPTO and the parties, the USPTO initially agreed with Consumer Watchdog and rejected all the claims in all three patents, however in response, WARF amended the claims of all three patents to make them more narrow, and in 2008 the USPTO found the amended claims in all three patents to be patentable. The decision on one of the patents (7,029,913) was appealable, while the decisions on the other two were not. Consumer Watchdog appealed the granting of the '913 patent to the USPTO's Board of Patent Appeals and Interferences (BPAI) which granted the appeal, and in 2010 the BPAI decided that the amended claims of the '913 patent were not patentable. However, WARF was able to re-open prosecution of the case and did so, amending the claims of the '913 patent again to make them more narrow, and in January 2013 the amended claims were allowed.
In July 2013, Consumer Watchdog announced that it would appeal the decision to allow the claims of the '913 patent to the US Court of Appeals for the Federal Circuit (CAFC), the federal appeals court that hears patent cases. At a hearing in December 2013, the CAFC raised the question of whether Consumer Watchdog had legal standing to appeal; the case could not proceed until that issue was resolved.
Diseases and conditions where stem cell treatment is being investigated include:
- Rheumatoid arthritis
- Parkinson's disease
- Alzheimer's disease
- Stroke and traumatic brain injury repair
- Learning disability due to congenital disorder 
- Spinal cord injury repair 
- Heart infarction 
- Anti-cancer treatments 
- Baldness reversal
- Replace missing teeth 
- Repair hearing 
- Restore vision  and repair damage to the cornea
- Amyotrophic lateral sclerosis 
- Crohn's disease 
- Wound healing 
- Male infertility due to absence of spermatogonial stem cells 
Research is underway to develop various sources for stem cells, and to apply stem cell treatments for neurodegenerative diseases and conditions, diabetes, heart disease, and other conditions. Research is also underway in generating organoids using stem cells, which would allow for further understanding of human development, organogenesis, and modeling of human diseases.
In more recent years, with the ability of scientists to isolate and culture embryonic stem cells, and with scientists' growing ability to create stem cells using somatic cell nuclear transfer and techniques to create induced pluripotent stem cells, controversy has crept in, both related to abortion politics and to human cloning.
Hepatotoxicity and drug-induced liver injury account for a substantial number of failures of new drugs in development and market withdrawal, highlighting the need for screening assays such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process.
- Cell bank
- Human genome
- Partial cloning
- Plant stem cell
- Stem cell controversy
- Stem cell marker
- Shinya Yamanaka
- Tuch BE (2006). "Stem cells – a clinical update". Australian Family Physician. 35 (9): 719–21. PMID 16969445.
- Becker AJ, McCulloch EA, Till JE (1963). "Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells". Nature. 197 (4866): 452–54. Bibcode:1963Natur.197..452B. doi:10.1038/197452a0. PMID 13970094.
- Siminovitch L, Mcculloch EA, Till JE (1963). "The distribution of colony-forming cells among spleen colonies". Journal of Cellular and Comparative Physiology. 62 (3): 327–36. doi:10.1002/jcp.1030620313. PMID 14086156.
- Schöler, Hans R. (2007). "The Potential of Stem Cells: An Inventory". In Nikolaus Knoepffler; Dagmar Schipanski; Stefan Lorenz Sorgner. Humanbiotechnology as Social Challenge. Ashgate Publishing. p. 28. ISBN 978-0-7546-5755-2.
- Mitalipov S, Wolf D (2009). "Totipotency, pluripotency and nuclear reprogramming". Adv. Biochem. Eng. Biotechnol. Advances in Biochemical Engineering/Biotechnology. 114: 185–99. Bibcode:2009esc..book..185M. doi:10.1007/10_2008_45. ISBN 978-3-540-88805-5. PMC . PMID 19343304.
- Ulloa-Montoya F, Verfaillie CM, Hu WS (2005). "Culture systems for pluripotent stem cells". J Biosci Bioeng. 100 (1): 12–27. doi:10.1263/jbb.100.12. PMID 16233846.
- Friedenstein AJ, Deriglasova UF, Kulagina NN, Panasuk AF, Rudakowa SF, Luriá EA, Ruadkow IA (1974). "Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method". Experimental Hematology. 2 (2): 83–92. ISSN 0301-472X. PMID 4455512.
- Friedenstein AJ, Gorskaja JF, Kulagina NN (1976). "Fibroblast precursors in normal and irradiated mouse hematopoietic organs". Experimental Hematology. 4 (5): 267–74. PMID 976387.
- Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998). "Blastocysts Embryonic Stem Cell Lines Derived from Human". Science. 282 (5391): 1145–47. Bibcode:1998Sci...282.1145T. doi:10.1126/science.282.5391.1145. PMID 9804556.
- Gilbert, Scott F.; College, Swarthmore; Helsinki, the University of (2014). Developmental biology (Tenth ed.). Sunderland, Mass.: Sinauer. ISBN 978-0878939787.
- Rakic, P (October 2009). "Evolution of the neocortex: a perspective from developmental biology". Nature Reviews. Neuroscience. 10 (10): 724–35. doi:10.1038/nrn2719. PMC . PMID 19763105.
- Noctor, SC; Flint, AC; Weissman, TA; Dammerman, RS; Kriegstein, AR (8 February 2001). "Neurons derived from radial glial cells establish radial units in neocortex". Nature. 409 (6821): 714–20. doi:10.1038/35055553. PMID 11217860.
- Ying, Q. L.; Wray, J; Nichols, J; Batlle-Morera, L; Doble, B; Woodgett, J; Cohen, P; Smith, A (2008). "The ground state of embryonic stem cell self-renewal". Nature. 453 (7194): 519–23. doi:10.1038/nature06968. PMC . PMID 18497825.
- "Culture of Human Embryonic Stem Cells (hESC)". National Institutes of Health. Archived from the original on 2010-01-06. Retrieved 2010-03-07.
- Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A (2003). "Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells". Cell. 113 (5): 643–55. doi:10.1016/S0092-8674(03)00392-1. PMID 12787505.
- Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA (2005). "Core transcriptional regulatory circuitry in human embryonic stem cells". Cell. 122 (6): 947–56. doi:10.1016/j.cell.2005.08.020. PMC . PMID 16153702.
- Adewumi O, Aflatoonian B, Ahrlund-Richter L, Amit M, Andrews PW, Beighton G, Bello PA, Benvenisty N, Berry LS, Bevan S, Blum B, Brooking J, Chen KG, Choo AB, Churchill GA, Corbel M, Damjanov I, Draper JS, Dvorak P, Emanuelsson K, Fleck RA, Ford A, Gertow K, Gertsenstein M, Gokhale PJ, Hamilton RS, Hampl A, Healy LE, Hovatta O, Hyllner J, Imreh MP, Itskovitz-Eldor J, Jackson J, Johnson JL, Jones M, Kee K, King BL, Knowles BB, Lako M, Lebrin F, Mallon BS, Manning D, Mayshar Y, McKay RD, Michalska AE, Mikkola M, Mileikovsky M, Minger SL, Moore HD, Mummery CL, Nagy A, Nakatsuji N, O'Brien CM, Oh SK, Olsson C, Otonkoski T, Park KY, Passier R, Patel H, Patel M, Pedersen R, Pera MF, Piekarczyk MS, Pera RA, Reubinoff BE, Robins AJ, Rossant J, Rugg-Gunn P, Schulz TC, Semb H, Sherrer ES, Siemen H, Stacey GN, Stojkovic M, Suemori H, Szatkiewicz J, Turetsky T, Tuuri T, van den Brink S, Vintersten K, Vuoristo S, Ward D, Weaver TA, Young LA, Zhang W (2007). "Characterization of human embryonic stem cell lines by the International Stem Cell Initiative". Nat. Biotechnol. 25 (7): 803–16. doi:10.1038/nbt1318. PMID 17572666.
- Ron Winslow (2009). "First Embryonic Stem-Cell Trial Gets Approval from the FDA". The Wall Street Journal. 23. January 2009.
- "Embryonic Stem Cell Therapy At Risk? Geron Ends Clinical Trial". ScienceDebate.com. Retrieved 2011-12-11.
- Wu DC, Boyd AS, Wood KJ (2007). "Embryonic stem cell transplantation: potential applicability in cell replacement therapy and regenerative medicine". Front Biosci. 12 (8–12): 4525–35. doi:10.2741/2407. PMID 17485394.
- Mahla RS (2016). "Stem cells application in regenerative medicine and disease threpeutics". International Journal of Cell Biology. 2016 (7): 19. doi:10.1155/2016/6940283. PMID 27516776.
- Ariff Bongso; Eng Hin Lee, eds. (2005). "Stem cells: their definition, classification and sources". Stem Cells: From Benchtop to Bedside. World Scientific. p. 5. ISBN 981-256-126-9. OCLC 443407924.
- Moore, K.L., T.V.N. Persaud, and A.G. Torchia. Before We Are Born: Essentials of Embryology and Birth Defects. Philadelphia, PA: Saunders, Elsevier. 2013. Print
- "Stem Cells" Mayo Clinic. Mayo foundation for medical education and research n.d Web. March 23, 2013
- Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002). "Pluripotency of mesenchymal stem cells derived from adult marrow". Nature. 418 (6893): 41–9. doi:10.1038/nature00870. PMID 12077603.
- Ratajczak MZ, Machalinski B, Wojakowski W, Ratajczak J, Kucia M (2007). "A hypothesis for an embryonic origin of pluripotent Oct-4(+) stem cells in adult bone marrow and other tissues". Leukemia. 21 (5): 860–7. doi:10.1038/sj.leu.2404630. PMID 17344915.
- Narasipura SD, Wojciechowski JC, Charles N, Liesveld JL, King MR (2008). "P-Selectin coated microtube for enrichment of CD34+ hematopoietic stem and progenitor cells from human bone marrow". Clin Chem. 54 (1): 77–85. doi:10.1373/clinchem.2007.089896. PMID 18024531.
- Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida K, Yamasaki T, Fujii Y, Okita K, Sakaida I (2006). "Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy". Stem Cells. 24 (10): 2292–8. doi:10.1634/stemcells.2005-0542. PMID 16778155.
- Subrammaniyan R, Amalorpavanathan J, Shankar R, et al. (September 2011). "Application of autologous bone marrow mononuclear cells in six patients with advanced chronic critical limb ischemia as a result of diabetes: our experience". Cytotherapy. 13 (8): 993–9. doi:10.3109/14653249.2011.579961. PMID 21671823.
- Madhusankar N. "Use of Bone Marrow derived Stem Cells in Patients with Cardiovascular Disorders". Journal of Stem Cells and Regenerative Medicine.
- Dedeepiya VD, Rao YY, Jayakrishnan GA, Parthiban JK, Baskar S, Manjunath SR, Senthilkumar R, Abraham SJ (2012). "Index of CD34+ Cells and Mononuclear Cells in the Bone Marrow of Spinal Cord Injury Patients of Different Age Groups: A Comparative Analysis". Bone Marrow Res. 2012: 787414. doi:10.1155/2012/787414. PMC . PMID 22830032.
- Gardner RL (2002). "Stem cells: potency, plasticity and public perception". Journal of Anatomy. 200 (3): 277–82. doi:10.1046/j.1469-7580.2002.00029.x. PMC . PMID 12033732.
- Behrens A, van Deursen JM, Rudolph KL, Schumacher B (2014). "Impact of genomic damage and ageing on stem cell function". Nat. Cell Biol. 16 (3): 201–7. doi:10.1038/ncb2928. PMC . PMID 24576896.
- Barrilleaux B, Phinney DG, Prockop DJ, O'Connor KC (2006). "Review: ex vivo engineering of living tissues with adult stem cells". Tissue Eng. 12 (11): 3007–19. doi:10.1089/ten.2006.12.3007. PMID 17518617.
- Gimble JM, Katz AJ, Bunnell BA (2007). "Adipose-derived stem cells for regenerative medicine". Circ Res. 100 (9): 1249–60. doi:10.1161/01.RES.0000265074.83288.09. PMID 17495232.
- Kuroda Y, Kitada M, Wakao S, Nishikawa K, Tanimura Y, Makinoshima H, Goda M, Akashi H, Inutsuka A, Niwa A, Shigemoto T, Nabeshima Y, Nakahata T, Nabeshima Y, Fujiyoshi Y, Dezawa M (2010). "Unique multipotent cells in adult human mesenchymal cell populations". Proc Natl Acad Sci U S A. 107 (19): 8639–43. Bibcode:2010PNAS..107.8639K. doi:10.1073/pnas.0911647107. PMC . PMID 20421459.
- "Bone Marrow Transplant". ucsfchildrenshospital.org.
- Kane, Ed (2008-05-01). "Stem-cell therapy shows promise for horse soft-tissue injury, disease". DVM Newsmagazine. Retrieved 2008-06-12.
- "Stem Cell FAQ". US Department of Health and Human Services. 2004-07-14. Archived from the original on 2009-01-09.
- De Coppi P, Bartsch G, Siddiqui MM, Xu T, Santos CC, Perin L, Mostoslavsky G, Serre AC, Snyder EY, Yoo JJ, Furth ME, Soker S, Atala A (2007). "Isolation of amniotic stem cell lines with potential for therapy". Nature Biotechnology. 25 (5): 100–106. doi:10.1038/nbt1274. PMID 17206138.
- "Vatican newspaper calls new stem cell source 'future of medicine' :: Catholic News Agency (CNA)". Catholic News Agency. 2010-02-03. Retrieved 2010-03-14.
- "European Biotech Company Biocell Center Opens First U.S. Facility for Preservation of Amniotic Stem Cells in Medford, Massachusetts". Reuters. 2009-10-22. Archived from the original on 2009-10-30. Retrieved 2010-03-14.
- "Europe's Biocell Center opens Medford office – Daily Business Update". The Boston Globe. 2009-10-22. Retrieved 2010-03-14.
- "The Ticker". BostonHerald.com. 2009-10-22. Retrieved 2010-03-14.
- "Biocell Center opens amniotic stem cell bank in Medford". Mass High Tech Business News. 2009-10-23. Retrieved 2012-08-26.
- "News » World's First Amniotic Stem Cell Bank Opens In Medford". wbur.org. Retrieved 2010-03-14.
- "Biocell Center Corporation Partners with New England's Largest Community-Based Hospital Network to Offer a Unique... – MEDFORD, Mass., March 8 /PRNewswire/". Massachusetts: Prnewswire.com. Retrieved 2010-03-14.
- "Making human embryonic stem cells". The Economist. 2007-11-22.
- Brand, Madeleine; Palca, Joe; Cohen, Alex (2007-11-20). "Skin Cells Can Become Embryonic Stem Cells". National Public Radio.
- "Breakthrough Set to Radically Change Stem Cell Debate". News Hour with Jim Lehrer. 2007-11-20.
- Kimbrel, E. A.; Lanza, R (2016). "Pluripotent stem cells: The last 10 years". Regenerative Medicine. 11 (8): 831–847. doi:10.2217/rme-2016-0117. PMID 27908220.
- Takahashi, K; Yamanaka, S (2006). "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors". Cell. 126 (4): 663–76. doi:10.1016/j.cell.2006.07.024. PMID 16904174.
- Takahashi, K; Tanabe, K; Ohnuki, M; Narita, M; Ichisaka, T; Tomoda, K; Yamanaka, S (2007). "Induction of pluripotent stem cells from adult human fibroblasts by defined factors". Cell. 131 (5): 861–72. doi:10.1016/j.cell.2007.11.019. PMID 18035408.
- Yu, J; Vodyanik, M. A.; Smuga-Otto, K; Antosiewicz-Bourget, J; Frane, J. L.; Tian, S; Nie, J; Jonsdottir, G. A.; Ruotti, V; Stewart, R; Slukvin, I. I.; Thomson, J. A. (2007). "Induced pluripotent stem cell lines derived from human somatic cells". Science. 318 (5858): 1917–20. doi:10.1126/science.1151526. PMID 18029452.
- "His inspiration comes from the research by Prof Shinya Yamanaka at Kyoto University, which suggests a way to create human embryo stem cells without the need for human eggs, which are in extremely short supply, and without the need to create and destroy human cloned embryos, which is bitterly opposed by the pro life movement."Highfield, Roger (2007-11-16). "Dolly creator Prof Ian Wilmut shuns cloning". London: The Telegraph.
- Robinton, D. A.; Daley, G. Q. (2012). "The promise of induced pluripotent stem cells in research and therapy". Nature. 481 (7381): 295–305. doi:10.1038/nature10761. PMC . PMID 22258608.
- Frozen blood a source of stem cells, study finds. newsdaily.com (2010-07-01)
- Beckmann J, Scheitza S, Wernet P, Fischer JC, Giebel B (2007). "Asymmetric cell division within the human hematopoietic stem and progenitor cell compartment: identification of asymmetrically segregating proteins". Blood. 109 (12): 5494–501. doi:10.1182/blood-2006-11-055921. PMID 17332245.
- Xie T, Spradling AC (1998). "decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary". Cell. 94 (2): 251–60. doi:10.1016/S0092-8674(00)81424-5. PMID 9695953.
- Song X, Zhu CH, Doan C, Xie T (2002). "Germline stem cells anchored by adherens junctions in the Drosophila ovary niches". Science. 296 (5574): 1855–7. Bibcode:2002Sci...296.1855S. doi:10.1126/science.1069871. PMID 12052957.
- Ian Murnaghan for Explore Stem Cells. Updated: 16 December 2013 Why Perform a Stem Cell Transplant?
- Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation In National Cancer Institute Fact Sheet web site. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2010. Cited August 24, 2010
- Moore, Keith L., T.V.N. Persaud, and Mark G. Torchia. Before We Are Born: Essentials of Embryology and Birth Defects. Philadelphia, PA: Saunders, Elsevier. 2013 Print.
- Bernadine Healy, M.D.. "Why Embryonic Stem Cells are obsolete" US News and world report. Retrieved on Aug 17, 2015.
- "Fetal Stem Cells Cause Tumor in a Teenage Boy".
- Regalado, Antonio, David P. Hamilton (July 2006). "How a University's Patents May Limit Stem-Cell Researcher." The Wall Street Journal. Retrieved on July 24, 2006.
- Stephen Jenei for Patent Baristas, April 3, 2007 WARF Stem Cell Patents Knocked Down in Round One
- Stephen Jenei for Patent Baristas, March 3, 2008 Ding! WARF Wins Round 2 As Stem Cell Patent Upheld
- Constance Holden for Science Now. March 12, 2008 WARF Goes 3 for 3 on Patents
- Stephen G. Kunin for Patents Post Grant. May 10, 2010 BPAI Rejects WARF Stem Cell Patent Claims in Inter Partes Reexamination Appeal
- United States Patent And Trademark Office. Board Of Patent Appeals and Interferences. The Foundation For Taxpayer & Consumer Rights, Requester And Appellant V. Patent Of Wisconsin Alumni Research Foundation, Patent Owner And Respondent. Appeal 2012-011693, Reexamination Control 95/000,154. Patent 7,029,913 Decision on Appeal Archived 2013-02-20 at the Wayback Machine.
- GenomeWeb staff, July 03, 2013 Consumer Watchdog, PPF Seek Invalidation of WARF's Stem Cell Patent
- Antoinette Konski for Personalized Medicine Bulletin. February 3, 2014 U.S. Government and USPTO Urges Federal Circuit to Dismiss Stem Cell Appeal
- Stem Cell Basics: What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized?. In Stem Cell Information World Wide Web site. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2009. cited Sunday, April 26, 2009
- Steinberg, Douglas (November 2000) Stem Cells Tapped to Replenish Organs thescientist.com
- ISRAEL21c: Israeli scientists reverse brain birth defects using stem cells December 25, 2008. (Researchers from the Hebrew University of Jerusalem-Hadassah Medical led by Prof. Joseph Yanai)
- Kang KS, Kim SW, Oh YH, Yu JW, Kim KY, Park HK, Song CH, Han H (2005). "A 37-year-old spinal cord-injured female patient, transplanted of multipotent stem cells from human UC blood, with improved sensory perception and mobility, both functionally and morphologically: a case study". Cytotherapy. 7 (4): 368–73. doi:10.1080/14653240500238160. PMID 16162459.
- Strauer BE, Schannwell CM, Brehm M (2009). "Therapeutic potentials of stem cells in cardiac diseases". Minerva Cardioangiol. 57 (2): 249–67. PMID 19274033.
- Stem Cells Tapped to Replenish Organs thescientist.com, Nov 2000. By Douglas Steinberg
- Hair Cloning Nears Reality as Baldness Cure WebMD November 2004
- Yen AH, Sharpe PT (2008). "Stem cells and tooth tissue engineering". Cell Tissue Res. 331 (1): 359–72. doi:10.1007/s00441-007-0467-6. PMID 17938970.
- "Gene therapy is first deafness 'cure'". New Scientist. February 14, 2005.
- "Stem cells used to restore vision". BBC News.
- Hanson, Charles; Hardarson, Thorir; Ellerström, Catharina; Nordberg, Markus; Caisander, Gunilla; Rao, Mahendra; Hyllner, Johan; Stenevi, Ulf (2013-03-01). "Transplantation of human embryonic stem cells onto a partially wounded human cornea in vitro". Acta Ophthalmologica. 91 (2): 127–130. doi:10.1111/j.1755-3768.2011.02358.x. ISSN 1755-3768. PMC . PMID 22280565.
- Vastag B (2001). "Stem Cells Step Closer to the Clinic: Paralysis Partially Reversed in Rats with ALS-like Disease". JAMA: The Journal of the American Medical Association. 285 (13): 1691–1693. doi:10.1001/jama.285.13.1691. PMID 11277806.
- Anderson, Querida (2008-06-15). "Osiris Trumpets Its Adult Stem Cell Product". Genetic Engineering & Biotechnology News. Mary Ann Liebert, Inc. p. 13. Retrieved 2008-07-06.
(subtitle) Procymal is being developed in many indications, GvHD being the most advanced
- Gurtner GC, Callaghan MJ, Longaker MT (2007). "Progress and potential for regenerative medicine". Annu. Rev. Med. 58: 299–312. doi:10.1146/annurev.med.58.082405.095329. PMID 17076602. Bone marrow transplantation is, as of 2009, the only established use of stem cells.
- Hanna V, Gassei K, Orwig KE (2015). "Stem Cell Therapies for Male Infertility: Where Are We Now and Where Are We Going?". Biennial Review of Infertility. Bone marrow transplantation is, as of 2009, the only established use of stem cells.
- Bubela T, Li MD, Hafez M, Bieber M, Atkins H (2012). "Is belief larger than fact: Expectations, optimism and reality for translational stem cell research". BMC Med. 10: 133. doi:10.1186/1741-7015-10-133. PMC . PMID 23131007.
- Ader, M., & Tanaka, E. M. (2014). Modeling human development in 3D culture. Current Opinion in Cell Biology, 31, 23-28. doi:10.1016/j.ceb.2014.06.013
- Greenhough S, Hay DC (2012). "Stem Cell-Based Toxicity Screening: Recent Advances in Hepatocyte Generation". Pharm Med. 26 (2): 85–89. doi:10.1007/BF03256896.
|Wikimedia Commons has media related to Stem cells.|
|Library resources about
- Stem Cell Basics Courtesy of the National Institutes of Health
- Nature Reports Stem Cells: Introductory material, research advances and debates concerning stem cell research.
- Understanding Stem Cells: A View of the Science and Issues from the National Academies