Editing Stem cell (section)

==Adult==
{{Main|Adult stem cell}}

[[Image:Stem cell division and differentiation.svg|thumb|Stem cell division and differentiation A:&nbsp;stem cell; B:&nbsp;progenitor cell; C:&nbsp;differentiated cell; 1:&nbsp;symmetric stem cell division; 2:&nbsp;asymmetric stem cell division; 3:&nbsp;progenitor division; 4:&nbsp;terminal differentiation]]

Adult stem cells, also called [[Somatic (biology)|somatic]] (from Greek σωματικóς, "of the body") stem cells, are stem cells which maintain and repair the tissue in which they are found.<ref>{{cite web |title=What is a stem cell |url=https://www.anthonynolan.org/patients-and-families/understanding-stem-cell-transplants/what-is-a-stem-cell |website=anthonynolan.org |publisher=Anthony Nolan |access-date=17 February 2022}}</ref>

There are three known accessible sources of [[autologous]] adult stem cells in humans:
# [[Bone marrow]], which requires extraction by ''harvesting'', usually from pelvic bones via surgery.<ref>{{Cite web|title=Bone marrow (stem cell) donation: MedlinePlus Medical Encyclopedia|url=https://medlineplus.gov/ency/patientinstructions/000839.htm|access-date=2021-10-17|website=medlineplus.gov|language=en}}</ref>
# Adipose tissue (fat cells), which requires extraction by liposuction.<ref>{{cite journal | vauthors = Coughlin RP, Oldweiler A, Mickelson DT, Moorman CT | title = Adipose-Derived Stem Cell Transplant Technique for Degenerative Joint Disease | journal = Arthroscopy Techniques | volume = 6 | issue = 5 | pages = e1761–e1766 | date = October 2017 | pmid = 29399463 | pmc = 5795060 | doi = 10.1016/j.eats.2017.06.048 }}</ref>
# 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.<ref>{{Cite web |date=2011-02-02 |title=autologous stem cell transplant |url=https://www.cancer.gov/publications/dictionaries/cancer-terms/def/autologous-stem-cell-transplant |access-date=2022-06-26 |website=www.cancer.gov |language=en}}</ref>
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 their own blood for elective surgical procedures.{{citation needed|date=August 2021}}

Pluripotent adult stem cells are rare and generally small in number, but they can be found in umbilical cord blood and other tissues.<ref>{{cite journal | vauthors = Ratajczak MZ, Machalinski B, Wojakowski W, Ratajczak J, Kucia M | title = A hypothesis for an embryonic origin of pluripotent Oct-4(+) stem cells in adult bone marrow and other tissues | journal = Leukemia | volume = 21 | issue = 5 | pages = 860–867 | date = May 2007 | pmid = 17344915 | doi = 10.1038/sj.leu.2404630 | s2cid = 21433689 | doi-access =  }}</ref> [[Bone marrow]] is a rich source of adult stem cells,<ref>{{cite journal | vauthors = Narasipura SD, Wojciechowski JC, Charles N, Liesveld JL, King MR | title = P-Selectin coated microtube for enrichment of CD34+ hematopoietic stem and progenitor cells from human bone marrow | journal = Clinical Chemistry | volume = 54 | issue = 1 | pages = 77–85 | date = January 2008 | pmid = 18024531 | doi = 10.1373/clinchem.2007.089896 | doi-access = free }}</ref> which have been used in treating several conditions including liver cirrhosis,<ref>{{cite journal | vauthors = Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida K, Yamasaki T, Fujii Y, Okita K, Sakaida I | title = Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy | journal = Stem Cells | volume = 24 | issue = 10 | pages = 2292–2298 | date = October 2006 | pmid = 16778155 | doi = 10.1634/stemcells.2005-0542 | s2cid = 5649484 }}</ref> chronic limb ischemia<ref>{{cite journal | vauthors = Subrammaniyan R, Amalorpavanathan J, Shankar R, Rajkumar M, Baskar S, Manjunath SR, Senthilkumar R, Murugan P, Srinivasan VR, Abraham S | title = Application of autologous bone marrow mononuclear cells in six patients with advanced chronic critical limb ischemia as a result of diabetes: our experience | journal = Cytotherapy | volume = 13 | issue = 8 | pages = 993–999 | date = September 2011 | pmid = 21671823 | doi = 10.3109/14653249.2011.579961 | s2cid = 27251276 }}</ref> and endstage heart failure.<ref>{{cite journal |url=http://www.pubstemcell.com/monthly/003010700010.htm | vauthors = Madhusankar N | title = Use of Bone Marrow derived Stem Cells in Patients with Cardiovascular Disorders | journal = Journal of Stem Cells and Regenerative Medicine | year = 2007 | volume = 3 | issue = 1 | pages = 28–29 | pmid = 24693021 | pmc = 3908115 }}</ref> The quantity of bone marrow stem cells declines with age and is greater in males than females during reproductive years.<ref>{{cite journal | vauthors = Dedeepiya VD, Rao YY, Jayakrishnan GA, Parthiban JK, Baskar S, Manjunath SR, Senthilkumar R, Abraham SJ | title = Index of CD34+ Cells and Mononuclear Cells in the Bone Marrow of Spinal Cord Injury Patients of Different Age Groups: A Comparative Analysis | journal = Bone Marrow Research | volume = 2012 | pages = 1–8 | year = 2012 | pmid = 22830032 | pmc = 3398573 | doi = 10.1155/2012/787414 | doi-access = free }}</ref> Much adult stem cell research to date has aimed to characterize their potency and self-renewal capabilities.<ref>{{cite journal | vauthors = Gardner RL | title = Stem cells: potency, plasticity and public perception | journal = Journal of Anatomy | volume = 200 | issue = Pt 3 | pages = 277–282 | date = March 2002 | pmid = 12033732 | pmc = 1570679 | doi = 10.1046/j.1469-7580.2002.00029.x }}</ref>   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]]).<ref name="pmid24576896">{{cite journal | vauthors = Behrens A, van Deursen JM, Rudolph KL, Schumacher B | title = Impact of genomic damage and ageing on stem cell function | journal = Nature Cell Biology | volume = 16 | issue = 3 | pages = 201–207 | date = March 2014 | pmid = 24576896 | pmc = 4214082 | doi = 10.1038/ncb2928 }}</ref>

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.).<ref>{{cite journal | vauthors = Barrilleaux B, Phinney DG, Prockop DJ, O'Connor KC | title = Review: ex vivo engineering of living tissues with adult stem cells | journal = Tissue Engineering | volume = 12 | issue = 11 | pages = 3007–3019 | date = November 2006 | pmid = 17518617 | doi = 10.1089/ten.2006.12.3007 | citeseerx = 10.1.1.328.2873 }}</ref><ref>{{cite journal | vauthors = Gimble JM, Katz AJ, Bunnell BA | title = Adipose-derived stem cells for regenerative medicine | journal = Circulation Research | volume = 100 | issue = 9 | pages = 1249–1260 | date = May 2007 | pmid = 17495232 | pmc = 5679280 | doi = 10.1161/01.RES.0000265074.83288.09 }}</ref> [[Muse cell]]s (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 CD90, [[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 [[Homeobox protein NANOG|Nanog]].<ref name=Kuroda>{{cite journal | vauthors = 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 | title = Unique multipotent cells in adult human mesenchymal cell populations | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 19 | pages = 8639–8643 | date = May 2010 | pmid = 20421459 | pmc = 2889306 | doi = 10.1073/pnas.0911647107 | bibcode = 2010PNAS..107.8639K | doi-access = free }}</ref>

Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants.<ref>{{cite web |url=http://www.ucsfchildrenshospital.org/treatments/leukemia_treatment_options/index.html |title=Bone Marrow Transplant|work=ucsfchildrenshospital.org}}</ref> Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses.<ref>{{cite news |first=Ed |last=Kane |title=Stem-cell therapy shows promise for horse soft-tissue injury, disease |url=http://veterinarynews.dvm360.com/dvm/Equine+Medicine/Stem-cell-therapy-shows-promise-for-horse-soft-tis/ArticleStandard/Article/detail/515503 |publisher=DVM Newsmagazine |date=2008-05-01 |access-date=2008-06-12 |archive-date=2008-12-11 |archive-url=https://web.archive.org/web/20081211094448/http://veterinarynews.dvm360.com/dvm/Equine+Medicine/Stem-cell-therapy-shows-promise-for-horse-soft-tis/ArticleStandard/Article/detail/515503 |url-status=dead }}</ref>

The use of adult stem cells in research and therapy is not as [[Stem cell controversy|controversial]] as the use of [[embryonic stem cell]]s, 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.<ref>{{cite web |url=https://www.hhs.gov/news/press/2004pres/20040714b.html |archive-url=https://web.archive.org/web/20090109104735/http://www.hhs.gov/news/press/2004pres/20040714b.html |archive-date=2009-01-09 |publisher=US Department of Health and Human Services |title=Stem Cell FAQ |date=2004-07-14}}</ref>

With the increasing demand of human adult stem cells for both research and clinical purposes (typically 1–5 million cells per kg of body weight are required per treatment) it becomes of utmost importance to bridge the gap between the need to expand the cells in vitro and the capability of harnessing the factors underlying replicative senescence. Adult stem cells are known to have a limited lifespan in vitro and to enter replicative senescence almost undetectably upon starting in vitro culturing.<ref name=Oliveira>{{cite journal | vauthors = Oliveira PH, da Silva CL, Cabral JM | title = Genomic Instability in Human Stem Cells: Current Status and Future Challenges | journal = Stem Cells | volume = 32 | issue = 11 | pages = 2824–2832 | date = 2014 | doi = 10.1002/stem.1796 | pmid = 25078438 | s2cid = 41335566 | doi-access = free }}</ref>

===Hematopoietic stem cells===

[[Hematopoietic stem cell]]s (HSCs) are vulnerable to [[DNA damage (naturally occurring)|DNA damage]] and [[mutation]]s that increase with age.<ref name="Zhang2020">Zhang L, Mack R, Breslin P, Zhang J. Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches. J Hematol Oncol. 2020 Nov 23;13(1):157. doi: 10.1186/s13045-020-00994-z. PMID 33228751; PMCID: PMC7686726</ref> This vulnerability may explain the increased risk of slow growing blood cancers (myeloid malignancies) in the elderly.<ref name = Zhang2020/>  Several factors appear to influence HSC aging including responses to the production of [[reactive oxygen species]] that may cause DNA damage and genetic mutations as well as altered [[epigenetics|epigenetic]] profiling.<ref>Montazersaheb S, Ehsani A, Fathi E, Farahzadi R. Cellular and Molecular Mechanisms Involved in Hematopoietic Stem Cell Aging as a Clinical Prospect. Oxid Med Cell Longev. 2022 Apr 1;2022:2713483. doi: 10.1155/2022/2713483. PMID 35401928; PMCID: PMC8993567</ref>