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Adult stem cell


Adult stem cells are undifferentiated cells found throughout the body after embryonic development that divide to replenish dying cells and regenerate damaged tissues. Also known as somatic (from Greek Σωματικóς, of the body) stem cells, they can be found in children, as well as adults.

Research into adult stem cells has been fueled by their abilities to divide or self-renew indefinitely and generate all the cell types of the organ from which they originate — potentially regenerating the entire organ from a few cells. Unlike embryonic stem cells, the use of adult stem cells in research and therapy is not controversial because the production of adult stem cells does not require the destruction of an embryo. Adult stem cells can be isolated from a tissue sample obtained from an adult. They have mainly been studied in humans and model organisms such as mice and rats.


Adult stem cell therapies

Main article: Stem cell treatments

Due to the ability of adult stem cells to be harvested from the patient, their therapeutic potential is the focus of much research. [1] [2] [3] Adult stem cells, similar to embryonic stem cells, have the ability to differentiate into more than one cell type, but unlike embryonic stem cells they are often restricted to certain lineages. The ability of a stem cell of one lineage to become another lineage is called transdifferentiation. Different types of adult stem cells are capable of transdifferentiation more than others, and for many there is no evidence of its occurrence. Consequently, adult stem therapies require a stem cell source of the specific lineage needed and harvesting and or culturing them up to the numbers required is a challenge. [4] [5]

Pluripotent adult stem cells can be found in a number of tissues including umbilical cord blood.[6] Using genetic reprogramming, pluripotent stem cells equivalent to embryonic stem cells have been derived from human adult skin tissue.[7][8][9] [10][11] Other 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, etc.).[12][13]

A great deal of adult stem cell research has focused on clarifying their capacity to divide or self-renew indefinitely and their differentiation potential.[14] In mice, pluripotent stem cells can be directly generated from adult fibroblast cultures.[15]

Adult stem cell treatments have been used for many years to treat successfully leukemia and related bone/blood cancers through bone marrow transplants.[16] The use of adult stem cells in research and therapy is not as controversial as embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Consequently, more US government funding is being provided for adult stem cell research[17].

Adult Stem Cell and Cancer

In recent years the concept of adult stem cell has transformed to include the theory that stem cells reside in many adult tissues and that these unique reservoir of adult stem cells are not only responsible for the normal reparative and regenerative processes but are also considered to be a prime target for genetic and epigenetic changes culminating to many abnormal conditions including cancer[3][4]. .


Defining properties

The rigorous 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.
  • Multipotency or multidifferentiative potential - the ability to generate progeny of several distinct cell types, for example both glial cells and neurons, opposed to unipotency - restriction to a single-cell type. Some researchers do not consider this property essential and believe that unipotent self-renewing stem cells can exist.

These properties can be illustrated with relative ease in vitro, using methods such as clonogenic assays, where the progeny of single cell is characterized. However, in vitro cell culture conditions can alter the behavior of cells. Proving that a particular subpopulation of cells possesses stem cell properties in vivo is challenging. Considerable debate exists whether some proposed cell populations in the adult are indeed stem cells.


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. Progentiors can go through several rounds of cell division before terminally differentiating into a mature cell. It is believed that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.

Multidrug resistance

Adult stem cells express transporters of the ATP-binding cassette family that actively pump a diversity of organic molecules out of the cell.[18] Many pharmaceuticals are exported by these transporters conferring multidrug resistance onto the cell. This complicates the design of drugs, for instance neural stem cell targeted therapies for the treatment of clinical depression.

Signaling pathways

Adult stem cell research has been focused on uncovering the general molecular mechanisms that control their self-renewal and differentiation.

  • Bmi-1
The transcriptional repressor Bmi-1 is one of the Polycomb-group proteins that was discovered as a common oncogene activated in lymphoma[19] and later shown to specifically regulate HSCs[20]. The role of Bmi-1 has also been illustrated in neural stem cells.[21]
  • Notch
The Notch pathway has been known to developmental biologists for decades. Its role in control of stem cell proliferation has now been demonstrated for several cell types including haematopoietic, neural and mammary[22] stem cells.
These developmental pathways are also strongly implicated as stem cell regulators.[23]


Under special conditions tissue-specific adult stem cells can generate a whole spectrum of cell types of other tissues, even crossing germ layers.[24] This phenomenon is referred to as stem cell transdifferentiation or plasticity. It can be induced by modifying the growth medium when stem cells are cultured in vitro or transplanting them to an organ of the body different from the one they were originally isolated from. There is yet no consensus among biologists on the prevalence and physiological and therapeutic relevance of stem cell plasticity.


Adipose derived adult stem cells

Adipose-derived stem cells (ASCs) have also been isolated from human fat, usually by method of liposuction. This cell population seems to be similar in many ways to mesenchymal stem cells (MSCs) derived from bone marrow. However, it is possible to isolate many more cells from adipose tissue and the harvest procedure itself is less painful than the harvest of bone marrow. Human ASCs have been shown to differentiate in the lab into bone, cartilage, fat, and muscle, while ASCs from rats have been converted to neurons[25], which makes ASCs a possible source for future applications in the clinic.[26][27] In support of this, current studies in animals suggest that ASCs might be able to repair significant bony defects and ASCs have been recently used to successfully repair a large cranial defect in a human patient. [28]

Induced pluripotent stem cells derived from epithelial cells

These are not adult stem cells, but rather reprogrammed epithelial cells with pluripotent capabilities. Using genetic reprogramming with protein transcription factors, pluripotent stem cells equivalent to embryonic stem cells have been derived from human adult skin tissue. [9][29] [30]Shinya Yamanaka and his colleagues at Kyoto University used the transcription factors Oct3/4, Sox2, c-Myc, and Klf4 [9] in their experiments on cells from human faces. Junying Yu, James Thompson, and their colleagues at the University of Wisconsin-Madison used a different set of factors, Oct4, Sox2, Nanog and Lin28 [9], and carried out their experiments using cells from human foreskin.

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 theraputic cloning as a venue of research.[31]

Haematopoietic stem cells

Haematopoietic stem cells give rise to all the blood cell types and are found in the bone marrow.

Mammary stem cells

Mammary stem cells provide the source of cells for growth of the mammary gland during puberty and gestation and play an important role in carcinogenesis of the breast.[32] Mammary stem cells have been isolated from human and mouse tissue as well as from cell lines derived from the mammary gland. A single such cell can give rise to both luminal and myoepithelial cell types of the gland and has been shown to regenerate the entire organ in mice.[33]

Mesenchymal stem cells

Main article: Mesenchymal stem cell

Mesenchymal stem cells differentiate into connective tissue, and are found in the bone marrow.

Endothelial stem cells

Main article: Endothelial stem cell

Neural stem cells

The existence of stem cells in the adult brain has been postulated following the discovery that the process of neurogenesis, birth of new neurons, continues into adulthood in rats.[34] It has since been shown that new neurons are generated in adult mice, songbirds and primates, including humans. Normally adult neurogenesis is restricted to the subventricular zone, which lines the lateral ventricles of the brain, and the dentate gyrus of the hippocampal formation.[35] Although the generation of new neurons in the hippocampus is well established, the presence of true self-renewing stem cells there has been debated.[36] Under certain circumstances, such as following tissue damage in ischemia, neurogenesis can be induced in other brain regions, including the neocortex.

Neural stem cells are commonly cultured in vitro as so called neurospheres - floating heterogeneous aggregates of cells, containing a large proportion of stem cells.[37] They can be propagated for extended periods of time and differentiated into both neuronal and glia cells, and therefore behave as stem cells. However, some recent studies suggest that this behaviour is induced by the culture conditions in progenitor cells, the progeny of stem cell division that normally undergo a strictly limited number of replication cycles in vivo.[38] Furthermore, neurosphere-derived cells do not behave as stem cells when transplanted back into the brain.[39]

Neural stem cells share many properties with haematopoietic stem cells (HSCs). Remarkably, when injected into the blood, neurosphere-derived cells differentiate into various cell types of the immune system.[40] Cells that resemble neural stem cells have been found in the bone marrow, the home of HSCs.[41] It has been suggested that new neurons in the dentate gyrus arise from circulating HCSs. Indeed, newborn cells first appear in the dentate in the heavily vascularised subgranular zone immediately adjacent to blood vessels.

Olfactory adult stem cells

Olfactory adult stem cells have been successfully harvested from the human olfactory mucosa cells, the lining of the nose involved in the sense of smell.[42]

Adult stem cells isolated from the olfactory mucosa (cells lining the inside of the nose involved in the sense of smell) have the ability to develop into many different cell types if they are given the right chemical environment.
These adult olfactory stem cells appear to have the same ability as embryonic stem cells in giving rise to many different cell types but have the advantage that they can be obtained from all individuals, even older people who might be most in need of stem cell therapies.

Olfactory stem cells hold potential for therapeutic applications. Thanks to their location they can be harvested with ease without harm to the patient in contrast to neural stem cells.

Testicular cells

Multipotent stem cells with a claimed equivalency to embryonic stem cells have been derived from spermatogonial progenitor cells found in the testicles of laboratory mice by scientists in Germany[43][44][45] and the United States. [46][47][48][49]. Multipotent stem cells have also been derived from germ cells found in human testicles.[50]

Open questions in adult stem cell research

  • How do adult stem cells arise? Are they residual embryonic stem cells? If so, what has stopped them differentiating: why are they still stem cells when most cells have differentiated?
  • Are stem cells found in different tissues fundamentally distinct, or is there a universal adult stem cell? Stem cells derived from different adult tissue can have remarkably similar properties. Research on adult stem cells has revealed that they can be induced to produce cell types of a variety of tissues. Do some or all adult stem cells belong to a single lineage but behave differently depending on extracellular cues?
  • Which adult tissues harbor stem cells? Do tissues that apparently contain no stem cells rely on other sources of new cells, or is it a matter of time until stem cells are identified there?
  • What molecular factors enable stem cell plasticity? While a lot is known about the cellular qualities that accompany multi- and pluripotency, the molecular/genetic factors that determine these qualities remain unclear. Could knowledge of these mechanisms allow us to reverse the process of differentiation and restore embryonic stem cell properties in adult stem cells or even differentiated cells?

News and External links

  • NIH Stem Cell Information Resource, resource for stem cell research
  • Stem Cells, the international journal for cell differentiation and proliferation
  • Adult Stem Cells Info, scientific information resource
  • Stem Cell and Cord Blood information database
  • Check The Score, Successes of Adult Stem Cells vs. Embryonic Stem Cells
  • whaaz a science wiki site for updates on stem cells and other related topics
  • Regenecell Adult stem cell treatments worldwide
  • BrainStorm Cell Therapeutics Inc. Adult Stem Cell research center on potential cure for Parkinson's and ALS


  • Tulane University Centre for Gene Therapy, prepares and distributes marrow stromal cells for academic research
  • UMDNJ Stem Cell and Regnerative Medicine, provides educational materials and research resources


  1. ^ [Adult stem or progenitor cells in treatment for type 1 diabetes: current progress, Can J Surg, Vol. 50, No. 2, April 2007]
  2. ^ [Stem Cells: A Revolution in Therapeutics—Recent Advances in Stem Cell Biology and Their Therapeutic Applications in Regenerative Medicine and Cancer Therapies, Clinical Pharmacology & Therapeutics (2007) 82, 252–264;]
  3. ^ [Stem Cells and Their Potential in Cell-Based Cardiac Therapies,Progress in Cardiovascular Diseases Volume 49, Issue 6, May-June 2007, Pages 396-413]
  4. ^ [ADULT STEM CELL PLASTICITY: Fact or Artifact?, Annual Review of Cell and Developmental Biology Vol. 19: 1-22]
  5. ^ Versus Embryonic Stem Cells: Treatments, Science 8 June 2007:Vol. 316. no. 5830, pp. 1422 - 1423
  6. ^ 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.
  7. ^ Gina Kolata (2007-11-22). Man Who Helped Start Stem Cell War May End It. New York Times.
  8. ^ Gina Kolata (2007-11-21). Scientists Bypass Need for Embryo to Get Stem Cells. New York Times.
  9. ^ a b c d Me too, too - How to make human embryonic stem cells without destroying human embryos. The Economist (2007-11-22).
  10. ^ Anne McIlroy (2007-11-21). Stem-cell method hailed as 'massive breakthrough'. Globe and Mail.
  11. ^ Alice Park (2007-11-20). A Breakthrough on Stem Cells. Time Magazine.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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. PMID 12033732.
  15. ^ 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.
  16. ^ [1], Bone Marrow Transplant
  17. ^ [2],USDHHS Stem Cell FAQ 2004
  18. ^ Chaudhary PM and Roninson IB (1991). "Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells". Cell 66 (1): 85-94. Entrez PubMed 1712673
  19. ^ Haupt Y, Bath ML, Harris AW and Adams JM (1993). "bmi-1 transgene induces lymphomas and collaborates with myc in tumorigenesis". Oncogene 8: 3161-3164. Entrez PubMed 8414519
  20. ^ Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, Morrison SJ and Clarke MF (2003). "Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells". Nature 423: 302-305. Entrez PubMed 12714971
  21. ^ Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF and Morrison SJ (2003). "Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation". Nature 425: 962-967. Entrez PubMed 14574365
  22. ^ Dontu G, Jackson KW, McNicholas E, Kawamura MJ, Abdallah WM and Wicha MS (2004). "Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells". Breast Cancer Res 6: R605-615. Full text at PMC: 1064073
  23. ^ Beachy PA, Karhadkar SS and Berman DM (2004). "Tissue repair and stem cell renewal in carcinogenesis". Nature 432: 324-331. Entrez PubMed 15549094
  24. ^ Filip S, English D and Mokry J (2004). "Issues in stem cell plasticity". J Cell Mol Med 8 (4): 572-577. Entrez PubMed 15601587
  25. ^ New nerves grown from fat cells. BBC (2007-10-19).
  26. ^ Zuk PA, Zhu M, Mizuno H, Huang JI, Chaudhari S, Lorenz HP, Benhaim P and Hedrick MH (2001). "Mutilineage cells derived from human adipose tissue: a putative source of stem cells for tissue engineering". Tissue Engineering 7 (2): 211-216.
  27. ^ Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P and Hedrick MH (2002). "Human adipose tissue is a source of multipotent stem cells". Mol Biol Cell 13: 4279-4295.
  28. ^ Associated Press (2004-12-20). Stem cells from fat used to repair girl's skull. MSNBC.
  29. ^ Madeleine Brand, Joe Palca and Alex Cohen (2007-11-20). Skin Cells Can Become Embryonic Stem Cells. National Public Radio.
  30. ^ Breakthrough Set to Radically Change Stem Cell Debate. News Hour with Jim Lehrer (2007-11-20).
  31. ^ "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."Roger Highfield (2007-11-16). Dolly creator Prof Ian Wilmut shuns cloning. The Telegraph.
  32. ^ Liu S, Dontu G and Wicha MS (2005). "Mammary stem cells, self-renewal pathways, and carcinogenesis". Breast Cancer Res 7 (3): 86-95. Entrez PubMed 15987436
  33. ^ Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ and Visvader JE (2005). "Mammary stem cells, self-renewal pathways, and carcinogenesis". Breast Cancer Res 7 (3): 86-95. Entrez PubMed 15987436
  34. ^ Altman J and Das GD (1965). "Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats". J Comp Neurol 124 (3): 319-335. Entrez PubMed 5861717
  35. ^ Alvarez-Buylla A, Seri B, Doetsch F (2002). "Identification of neural stem cells in the adult vertebrate brain". Brain Res Bull 57 (6): 751-758. Entrez PubMed 12031271
  36. ^ Bull ND and Bartlett PF (2005). "The adult mouse hippocampal progenitor is neurogenic but not a stem cell". J Neurosci 25 (47): 10815-10821. Entrez PubMed 16306394
  37. ^ Reynolds BA and Weiss S (1992). "Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system". Science 255: 1707-1710. Entrez PubMed 1553558
  38. ^ Doetsch F, Petreanu L, Caille I, Garcia-Verdugo JM and Alvarez-Buylla A (2002). "EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells". Neuron 36 (6): 1021-1034. Entrez PubMed 12495619
  39. ^ Marshall GP 2nd, Laywell ED, Zheng T, Steindler DA and Scott EW (2006). "In vitro-derived "neural stem cells" function as neural progenitors without the capacity for self-renewal". Stem Cells 24 (3): 731-738. Entrez PubMed 16339644
  40. ^ Bjornson CR, Rietze RL, Reynolds BA, Magli MC and Vescovi AL (1999). "Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo". Science 283: 534-537. Entrez PubMed 9915700
  41. ^ Kucia M, Zhang YP, Reca R, Wysoczynski M, Machalinski B, Majka M, Ildstad ST, Ratajczak J, Shields CB and Ratajczak MZ (2006). "Cells enriched in markers of neural tissue-committed stem cells reside in the bone marrow and are mobilized into the peripheral blood following stroke". Leukemia 20 (1): 18-28. Entrez PubMed 16270036
  42. ^ Murrell W, Feron F, Wetzig A, Cameron N, Splatt K, Bellette B, Bianco J, Perry C, Lee G and Mackay-Sim A (2005). "Multipotent stem cells from adult olfactory mucosa". Dev Dyn 233 (2): 496-515. Entrez PubMed 15782416
  43. ^ Testicle cells may aid research. BBC (2006-03-25).
  44. ^ CBS/Associated Press (2006-03-24). Study: Mice Testes Act Like Stem Cells. CBS.
  45. ^ Rick Weiss (2006-03-25). Embryonic Stem Cell Success. Washington Post.
  46. ^ Promising New Source Of Stem Cells: Mouse Testes Produce Wide Range Of Tissue Types. Science Daily (2007-09-24).
  47. ^ Babara Miller (2007-09-20). Testicles yield stem cells in science breakthrough. Australian Broadcasting Corporation.
  48. ^ J.R. Minkel (2007-09-19). Testes May Prove Fertile Source of Stem Cells. Scientific American.
  49. ^ Stem Cells in Adult Testes Provide Alternative to Embryonic Stem Cells for Organ Regeneration. Cornell University (2007-09-20).
  50. ^ Maggie Fox (Reuters) (2006-04-02). U.S. Firm Says It Made Stem Cells From Human Testes. Washington Post.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Adult_stem_cell". A list of authors is available in Wikipedia.
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