User:Peter Znamenskiy/Adult stem cell

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Stem cell division and differentiation. A - stem cell; B - progenitor cell; C - differentiated cell; 1 - symmetric stem cell division; 2 - asymmetric stem cell division; 3 - progenitor division; 4 - terminal differentiation

Adult stem cells are undifferentiated cells found throughout the body that divide to replenish dying cells and regenerate damaged tissues. Also known as somatic (from Greek Σωματικóς, of the body) 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 handful of cells. 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. They can be isolated from a tissue sample obtained from an adult. Adult stem cells have mainly been studied in humans and model organisms such as mice and rats.

Properties[edit]

File:Stem cells transdiff.jpg
Plasticity of adult stem cells. Adult stem cells from some sources can produce cell types not found in their native tissue.

Defining properties[edit]

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.

Lineage[edit]

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-newal potential. Progentiors can go through several rounds of cell division before terminally differentiating into a mature cell. It is beleived 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[edit]

Adult stem cells express transporters of the ATP-binding cassette family that actively pump a diversity of organic molecules out of the cell. 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[edit]

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

  • Bmi-1
The Polycomb group transcriptional repressor Bmi-1 was discovered as a common oncogene activated in lymphoma[1] and later shown to specifically regulate HSCs[2]. The role of Bmi-1 has also been illustrated in neural stem cells.[3]
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[4] stem cells.
These developmental pathways are also strongly implicated as stem cell regulators.[5]

Plasticity[edit]

Under special conditions tissue-specific adult stem cells can generate a whole spectrum of cell types of other tissues, even crossing germ layers (see Plasticity of adult stem cells image).[6] 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 concensus among biologists on the prevalence and physiological and therapeutic relevance of stem cell plasticity.

Types[edit]

Adipose derived adult stem cells[edit]

Adipose derived adult stem (ADAS) cells have also been isolated from fat, usually by method of liposuction. This source of cells seems to be similar in many ways to mesenchymal stem cells (MSCs) derived from bone marrow, except that it is possible to isolate many more cells from fat. These cells have been shown to differentiate into bone, cartilage, fat, muscle, and neurons. These cells have been recently used to successfully repair a large cranial defect in a human patient [1].

Haematopoietic stem cells[edit]

Main article: Pluripotential hemopoietic stem cell

Mammary stem cells[edit]

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.[7] 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.[8]

Neural stem cells[edit]

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.[9] 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 subvetricular zone, which lines the lateral ventricles of the brain, and the dentate gyrus of the hippocampal formation.[10] Although the generation of new neurons in the hippocampus is well established, the presence of true self-renewing stem cells there has been debated.[11] 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.[12] 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 strickly limited number of replication cycles in vivo.[13] Furthermore, neurosphere-derived cells do not behave as stem cells when transplanted back into the brain.[14]

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.[15] Cells that resemble neural stem cells have been found in the bone marrow, the home of HSCs.[16] 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[edit]

Olfactory adult stem cells have been successfully from the cells harvested from the human olfactory mucosa, the lining of the nose involved in the sense of smell.[17]

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 to stem cell therapies.

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

Adult stem cell treatments[edit]

Main article: Stem cell treatments

Adult stem cells are being developed for use in treatments for a variety of human conditions, ranging from blindness to spinal cord injury. Since adult stem cells can be harvested from the patient, potential ethical issues and immunogenic rejection are averted. Although many different kinds of multipotent stem cells have been identified, adult stem cells that could give rise to all cell and tissue types have not yet been found. Adult stem cells are often present in only minute quantities and can therefore be difficult to isolate and purify. However, they can be multiplied in-vitro to therapeutic numbers. There is also limited evidence that adult stem cells may not have the same capacity to multiply as embryonic stem cells. Finally, adult stem cells may contain more DNA abnormalities—caused by sunlight, toxins, and errors in DNA replication the course of a lifetime. However, there are a number of clinically proven adult stem cell successes.

References[edit]

  1. ^ Haupt Y, Bath ML, Harris AW and Adams JM (1993). "bmi-1 transgene induces lymphomas and collaborates with myc in tumorigenesis". Oncogene. 8 (11): 3161–3164. PMID 8414519.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ 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 (6937): 302–305. doi:10.1038/nature01587. PMID 12714971.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ 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 (6961): 962–967. doi:10.1038/nature02060. PMC 2614897. PMID 14574365.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ 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 (6): R605–615. doi:10.1186/bcr920. PMC 1064073.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  5. ^ Beachy PA, Karhadkar SS and Berman DM (2004). "Tissue repair and stem cell renewal in carcinogenesis". Nature. 432 (7015): 324–331. doi:10.1038/nature03100. PMID 15549094.
  6. ^ Filip S, English D and Mokry J (2004). "Issues in stem cell plasticity". J Cell Mol Med. 8 (4): 572–577. doi:10.1111/j.1582-4934.2004.tb00483.x. PMID 15601587.
  7. ^ Liu S, Dontu G and Wicha MS (2005). "Mammary stem cells, self-renewal pathways, and carcinogenesis". Breast Cancer Res. 7 (3): 86–95. doi:10.1186/bcr1021. PMC 1143566. PMID 15987436.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  8. ^ 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. doi:10.1186/bcr1021. PMC 1143566. PMID 15987436.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  9. ^ Altman J and Das GD (1965). "Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats". J Comp Neurol. 124 (3): 319–335. doi:10.1002/cne.901240303. PMID 5861717.
  10. ^ 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. doi:10.1016/S0361-9230(01)00770-5. PMID 12031271.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ Bull ND and Bartlett PF (2005). "The adult mouse hippocampal progenitor is neurogenic but not a stem cell". J Neurosci. 25 (47): 10815–10821. doi:10.1523/JNEUROSCI.3249-05.2005. PMID 16306394.
  12. ^ Reynolds BA and Weiss S (1992). "Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system". Science. 255 (5052): 1707–1710. doi:10.1126/science.1553558. PMID 1553558.
  13. ^ 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. doi:10.1016/S0896-6273(02)01133-9. PMID 12495619.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ 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. doi:10.1634/stemcells.2005-0245. PMID 16339644.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
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  16. ^ 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. doi:10.1038/sj.leu.2404011. PMID 16270036.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ 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. doi:10.1002/dvdy.20360. PMID 16339644.{{cite journal}}: CS1 maint: multiple names: authors list (link)


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