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In [[multicellular organisms]], '''stem cells''' are [[Cellular differentiation|undifferentiated]] or partially differentiated [[Cell (biology)|cells]] that can change into various [[types of cells]] and [[Cell proliferation|proliferate]] indefinitely to produce more of the same stem cell. They are the earliest type of cell in a [[cell lineage]].<ref name=":7">{{cite book |last1=Atala |first1=Anthony |last2=Lanza |first2=Robert | name-list-style = vanc |url=
In [[mammals]], roughly 50 to 150 cells make up the [[inner cell mass]] during the [[blastocyst]] stage of [[embryonic development]], around days 5–14. These have stem-cell capability. ''[[In vivo]]'', they eventually differentiate into all of the body's cell types (making them [[pluripotent]]). This process starts with the differentiation into the three [[germ layers]] – the [[ectoderm]], [[mesoderm]] and [[endoderm]] – at the [[gastrulation]] stage. However, when they are isolated and [[Cell culture|cultured]] ''[[in vitro]]'', they can be kept in the stem-cell stage and are known as [[embryonic stem cells]] (ESCs).
[[Adult stem cells]] are found in a few select locations in the body, known as [[Stem-cell niche|niches]], such as those in the [[bone marrow]] or [[gonads]]. They exist to replenish rapidly lost cell types and are [[multipotent]] or unipotent, meaning they only differentiate into a few cell types or one type of cell. In mammals, they include, among others, [[hematopoietic stem cells]], which replenish blood and immune cells, [[Stratum basale|basal cells]], which maintain the skin [[epithelium]], and [[mesenchymal stem cells]], which maintain bone, [[cartilage]], muscle and fat cells. Adult stem cells are a small minority of cells; they are vastly outnumbered by the progenitor cells and terminally differentiated cells that they differentiate into.<ref name=":7" />{{rp||452}}
Research into stem cells grew out of findings by Canadian biologists [[Ernest McCulloch]], [[James Till]] and Andrew J. Becker at the [[University of Toronto]] and the Ontario Cancer Institute in the 1960s.<ref>{{cite journal |vauthors = Becker AJ, McCulloch EA, Till JE |title = Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells |journal = Nature |volume = 197 |issue = 4866 |pages = 452–454 |date = February 1963 |pmid = 13970094 |doi = 10.1038/197452a0 |bibcode = 1963Natur.197..452B |hdl-access = free |hdl = 1807/2779 |s2cid = 11106827 |issn = 0028-0836 }}</ref><ref>{{cite journal |vauthors = Siminovitch L, McCulloch EA, Till JE |title = The distribution of colony-forming cells among spleen colonies |journal = Journal of Cellular and Comparative Physiology |volume = 62 |issue = 3 |pages = 327–336 |date = December 1963 |pmid = 14086156 |doi = 10.1002/jcp.1030620313 |hdl-access = free |hdl = 1807/2778 |s2cid = 43875977 }}</ref> {{As of|2016|}}, the only established [[Stem-cell therapy|medical therapy using stem cells]] is [[hematopoietic stem cell transplantation]],<ref>{{cite journal |vauthors = Müller AM, Huppertz S, Henschler R |title = Hematopoietic Stem Cells in Regenerative Medicine: Astray or on the Path? |journal = Transfusion Medicine and Hemotherapy |volume = 43 |issue = 4 |pages = 247–254 |date = July 2016 |pmid = 27721700 |pmc = 5040947 |doi = 10.1159/000447748 }}</ref> first performed in 1958 by French oncologist [[Georges Mathé]]. Since 1998 however, it has been possible to culture and differentiate human embryonic stem cells (in [[stem-cell lines]]). The process of isolating these cells has been [[Stem cell controversy|controversial]], because it typically results in the destruction of the embryo. Sources for isolating ESCs have been [[Stem cell laws|restricted]] in some European countries and Canada, but others such as the UK and China have promoted the research.<ref name="Pew Intl">{{cite news |last1=Ralston |first1=Michelle |title=Stem Cell Research Around the World |url=https://www.pewforum.org/2008/07/17/stem-cell-research-around-the-world/ |work=Pew Research Center's Religion & Public Life Project |date=17 July 2008 }}</ref> [[Somatic cell nuclear transfer]] is a [[cloning]] method that can be used to create a cloned embryo for the use of its embryonic stem cells in stem cell therapy.<ref>{{cite journal |last1=Tuch |first1=B. E. |title=Stem cells: a clinical update |journal=Australian Family Physician |date=September 2006 |volume=35 |issue=9 |pages=719–721 |url=https://www.racgp.org.au/afp/200609/11021 |id={{ProQuest|216301343}} |pmid=16969445 }}</ref> In 2006, a Japanese team led by [[Shinya Yamanaka]] discovered a method to convert mature body cells back into stem cells. These were termed [[induced pluripotent stem cells]] (iPSCs).<ref name=":6" />
== History ==
The term ''stem cell'' was coined by [[Theodor Boveri]] and [[Valentin Haecker]] in late 19th century.<ref name="origin">{{cite journal |last1=Ramalho-Santos |first1=Miguel |last2=Willenbring |first2=Holger |title=On the Origin of the Term 'Stem Cell' |journal=Cell Stem Cell |date=June 2007 |volume=1 |issue=1 |pages=35–38 |doi=10.1016/j.stem.2007.05.013 |pmid=18371332 |doi-access=free }}</ref> Pioneering works in theory of blood stem cell were conducted in the beginning of 20th century by [[Artur Pappenheim]], [[Alexander A. Maximow]], [[Franz Ernst Christian Neumann]].<ref name="origin" />
The key properties of a stem cell were first defined by [[Ernest McCulloch]] and [[James Till]] at the University of Toronto and the Ontario Cancer Institute in the early 1960s. They discovered the blood-forming stem cell, the [[hematopoietic stem cell]] (HSC), through their pioneering work in mice. McCulloch and Till began a series of experiments in which bone marrow cells were injected into irradiated mice. They observed lumps in the spleens of the mice that were linearly proportional to the number of bone marrow cells injected. They hypothesized that each lump (colony) was a clone arising from a single marrow cell (stem cell). In subsequent work, McCulloch and Till, joined by graduate student [[Andrew John Becker]] and senior scientist [[Louis Siminovitch]], confirmed that each lump did in fact arise from a single cell. Their results were published in ''Nature'' in 1963. In that same year, Siminovitch was a lead investigator for studies that found colony-forming cells were capable of self-renewal, which is a key defining property of stem cells that Till and McCulloch had theorized.<ref>{{cite web|url=https://news.usask.ca/articles/research/2018/the-accidental-discovery-of-stem-cells.php|title =The Accidental Discovery of Stem Cells|last1=MacPherson|first1=Colleen|website=USask News|publisher=University of Saskatchewan|access-date=3 December 2019|ref=1|name-list-style=vanc}}</ref>
The first therapy using stem cells was a [[bone marrow transplant]] performed by French oncologist [[Georges Mathé]] in
In 1981, embryonic stem (ES) cells were first isolated and successfully cultured using mouse blastocysts by British biologists [[Martin Evans]] and [[Matthew Kaufman]]. This allowed the formation of murine genetic models, a system in which the genes of mice are deleted or altered in order to study their function in pathology. In 1991, a process that allowed the human stem cell to be isolated was patented by Ann Tsukamoto. By 1998, human embryonic stem cells were first isolated by American biologist [[James Thomson (cell biologist)|James Thomson]], which made it possible to have new transplantation methods or various cell types for testing new treatments. In 2006, [[Shinya Yamanaka]]'s team in Kyoto, Japan converted fibroblasts into pluripotent stem cells by modifying the expression of only four genes. The feat represents the origin of induced pluripotent stem cells, known as iPS cells.<ref name=":6">{{cite web|url=http://sitn.hms.harvard.edu/flash/2014/stem-cells-a-brief-history-and-outlook-2/|title=Stem Cells: A Brief History and Outlook|last1=Ferreira|first1=Leonardo|date=2014-01-03|website=Stem Cells: A Brief History and Outlook – Science in the News|publisher=WordPress|access-date=3 December 2019|ref=2|name-list-style=vanc}}</ref>
In 2011, a female [[maned wolf]], run over by a truck, underwent stem cell treatment at the
==Properties==
The classical definition of a stem cell requires that it possesses two properties:
* Self-renewal: the ability to go through numerous [[cell cycle|cycles]] of [[cell growth]] and [[cell division]], known as [[cell proliferation]], while maintaining the undifferentiated state.
* [[Cell potency|Potency]]: the capacity to [[Cellular differentiation|differentiate]] into specialized cell types. In the strictest sense, this requires stem cells to be either [[totipotency|totipotent]] or [[pluripotency|pluripotent]]—to be able to give rise to any mature cell type, although [[multipotent]] or [[unipotent cell|unipotent]] [[progenitor cell]]s are sometimes referred to as stem cells. Apart from this, it is said that stem cell function is regulated in a [[feedback]] mechanism.
===Self-renewal===
Two mechanisms ensure that a stem cell population is maintained (
1. [[Asymmetric cell division]]: a stem cell divides into one mother cell, which is identical to the original stem cell, and another daughter cell, which is differentiated.
When a stem cell self-renews, it divides and
H.
Stem cells use [[telomerase]], a protein that restores [[telomeres]], to protect their DNA and extend their cell division limit (the [[Hayflick limit]]).<ref>{{cite journal | vauthors = Cong YS, Wright WE, Shay JW | title = Human telomerase and its regulation | journal = Microbiology and Molecular Biology Reviews | volume = 66 | issue = 3 | pages = 407–425, table of contents | date = September 2002 | pmid = 12208997 | pmc = 120798 | doi = 10.1128/MMBR.66.3.407-425.2002 | doi-access = free }}</ref>
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[[Cell potency|Potency]] specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.<ref name=Schoeler>{{cite book |title=Humanbiotechnology as Social Challenge |editor1=Nikolaus Knoepffler |editor2=Dagmar Schipanski |editor3=Stefan Lorenz Sorgner |page=28 |chapter=The Potential of Stem Cells: An Inventory | last = Schöler | first = Hans R. | name-list-style = vanc |publisher=Ashgate Publishing|year=2007 |isbn=978-0-7546-5755-2}}</ref>
* [[Totipotency|Totipotent]] (also known as omnipotent) stem cells can differentiate into embryonic and extraembryonic cell types. Such cells can construct a complete, viable organism.<ref name=Schoeler/> These cells are produced from the [[Cell fusion|fusion]] of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent.<ref>{{cite book | vauthors = Mitalipov S, Wolf D | chapter = Totipotency, pluripotency and nuclear reprogramming | volume = 114 | pages = 185–199 | year = 2009 | pmid = 19343304 | pmc = 2752493 | doi = 10.1007/10_2008_45 | isbn = 978-3-540-88805-5 | series = Advances in Biochemical Engineering/Biotechnology | bibcode = 2009esc..book..185M | title = Engineering of Stem Cells | publisher = Springer }}</ref>
* [[Pluripotency|Pluripotent]] stem cells are the descendants of totipotent cells and can differentiate into nearly all cells,<ref name=Schoeler/> i.e. cells derived from any of the three [[germ layer]]s.<ref>{{cite journal | vauthors = Ulloa-Montoya F, Verfaillie CM, Hu WS | title = Culture systems for pluripotent stem cells | journal = Journal of Bioscience and Bioengineering | volume = 100 | issue = 1 | pages = 12–27 | date = July 2005 | pmid = 16233846 | doi = 10.1263/jbb.100.12 | url = https://lirias.kuleuven.be/handle/123456789/238336 }}</ref>
* [[Multipotency|Multipotent]] stem cells can differentiate into a number of cell types, but only those of a closely related family of cells.<ref name=Schoeler/>
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[[Embryonic stem cell]]s (ESCs) are the cells of the [[inner cell mass]] of a [[blastocyst]], formed prior to [[Implantation (human embryo)|implantation]] in the uterus.<ref>{{cite journal | vauthors = Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM | title = Embryonic stem cell lines derived from human blastocysts | journal = Science | volume = 282 | issue = 5391 | pages = 1145–1147 | date = November 1998 | pmid = 9804556 | doi = 10.1126/science.282.5391.1145 | bibcode = 1998Sci...282.1145T | doi-access = free }}</ref> In [[human embryonic development]] the [[blastocyst]] stage is reached 4–5 days after [[Human fertilization|fertilization]], at which time it consists of 50–150 cells. ESCs are [[pluripotent]] and give rise during development to all derivatives of the three [[germ layer]]s: [[ectoderm]], [[endoderm]] and [[mesoderm]]. In other words, they can develop into each of the more than 200 cell types of the adult [[human body|body]] when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the [[extraembryonic membrane]]s or to the [[placenta]].
During embryonic development the cells of the inner cell mass 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]] (CNS).<ref name="Developmental biology">{{cite book |last1=Gilbert |first1=Scott F. |title=Developmental Biology |date=2014 |publisher=Sinauer Associates |isbn=978-0-87893-978-7 }}{{Page needed|date=January 2019}}</ref> 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]].
The neural stem cells self-renew and at some point transition into [[radial glial cell|radial glial progenitor cells]] (RGPs). Early-formed RGPs self-renew by symmetrical division to form a reservoir group of [[progenitor cell]]s. These cells transition to a [[neurogenesis|neurogenic]] state and start to divide [[Asymmetric cell division|asymmetrically]] to produce a large diversity of many different neuron types, each with unique gene expression, morphological, and functional characteristics. The process of generating neurons from radial glial cells is called [[neurogenesis]]. The radial glial cell, has a distinctive bipolar morphology with highly elongated processes spanning the thickness of the neural tube wall. It shares some [[glial]] characteristics, most notably the expression of [[glial fibrillary acidic protein]] (GFAP).<ref>{{cite journal | vauthors = Rakic P | title = Evolution of the neocortex: a perspective from developmental biology | journal = Nature Reviews. Neuroscience | volume = 10 | issue = 10 | pages = 724–735 | date = October 2009 | pmid = 19763105 | pmc = 2913577 | doi = 10.1038/nrn2719 }}</ref><ref>{{cite journal | vauthors = Noctor SC, Flint AC, Weissman TA, Dammerman RS, Kriegstein AR | title = Neurons derived from radial glial cells establish radial units in neocortex | journal = Nature | volume = 409 | issue = 6821 | pages = 714–720 | date = February 2001 | pmid = 11217860 | doi = 10.1038/35055553 | bibcode = 2001Natur.409..714N | s2cid = 3041502 }}</ref> 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 ([[neuron]]s, [[astrocyte]]s, and [[oligodendrocyte]]s), and thus their potency is restricted.<ref name="Developmental biology"/>
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 [[Glycogen synthase kinase-3 beta|GSK3B]] and the [[MAPK/ERK pathway]], called 2i, has also been shown to maintain pluripotency in stem cell culture.<ref>{{cite journal | vauthors = Ying QL, Wray J, Nichols J, Batlle-Morera L, Doble B, Woodgett J, Cohen P, Smith A | title = The ground state of embryonic stem cell self-renewal | journal = Nature | volume = 453 | issue = 7194 | pages = 519–523 | date = May 2008 | pmid = 18497825 | pmc = 5328678 | doi = 10.1038/nature06968 | bibcode = 2008Natur.453..519Y }}</ref> Human ESCs are grown on a feeder layer of mouse embryonic [[fibroblasts]] and require the presence of basic fibroblast growth factor (bFGF or FGF-2).<ref>
{{cite web|url=http://stemcells.nih.gov/research/NIHresearch/scunit/culture.asp|archive-url=https://web.archive.org/web/20100106111652/http://stemcells.nih.gov/research/NIHresearch/scunit/culture.asp|archive-date=2010-01-06|title=Culture of Human Embryonic Stem Cells (hESC)|publisher=National Institutes of Health|access-date=2010-03-07}}</ref> Without optimal culture conditions or genetic manipulation,<ref>
{{cite journal | vauthors = Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A | title = Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells
▲{{cite journal | vauthors = Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A | title = Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells | journal = Cell | volume = 113 | issue = 5 | pages = 643–655 | date = May 2003 | pmid = 12787505 | doi = 10.1016/S0092-8674(03)00392-1 | hdl = 1842/843 | s2cid = 2236779 | hdl-access = free }}</ref> 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]], [[Homeobox protein NANOG|Nanog]], and [[Sox2]] form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.<ref>
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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 to discern complications of diseases, or to study cell reactions to proposed new drugs.
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.,<ref>{{cite journal | vauthors = Mahla RS | title = Stem Cells Applications in Regenerative Medicine and Disease Therapeutics | journal = International Journal of Cell Biology | volume = 2016 | issue = 7 | pages = 1–24 | year = 2016 | pmid = 27516776 | pmc = 4969512 | doi = 10.1155/2016/6940283 | doi-access = free }}</ref> however, there are currently no approved treatments using ES cells. The first human trial was approved by the US Food and Drug Administration in January 2009.<ref>{{cite news | first1 = Ron | last1 = Winslow | first2 = Alicia | last2 = Mundy | name-list-style = vanc |title= First Embryonic Stem-Cell Trial Gets Approval from the FDA |newspaper= The Wall Street Journal |url= https://www.wsj.com/articles/SB123268485825709415 |date= 23 January 2009 }}</ref> 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.<ref>{{cite web
<gallery>
File:Mouse embryonic stem cells.jpg| [[Mus musculus|Mouse]] [[Mammalian embryogenesis|embryonic]] stem cells with fluorescent marker
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=== Mesenchymal stem cells ===
{{Main|Mesenchymal stem cell}}
[[File:Human mesenchymal stem cells.gif|thumb|Human mesenchymal stem cells]]
Mesenchymal stem cells (MSC) or mesenchymal stromal cells, also known as medicinal signaling cells are known to be multipotent, which can be found in adult tissues, for example, in the muscle, liver, bone marrow and adipose tissue. Mesenchymal stem cells usually function as structural support in various organs as mentioned above, and control the movement of substances. MSC can differentiate into numerous cell categories as an illustration of adipocytes, osteocytes, and chondrocytes, derived by the mesodermal layer.<ref name="Mesenchymal and induced pluripotent">{{cite journal | vauthors = Zomer HD, Vidane AS, Gonçalves NN, Ambrósio CE | title = Mesenchymal and induced pluripotent stem cells: general insights and clinical perspectives | journal = Stem Cells and Cloning: Advances and Applications| volume = 8 | pages = 125–134 | date = 2015-09-28 | pmid = 26451119 | pmc = 4592031 | doi = 10.2147/SCCAA.S88036 | doi-access = free }}</ref> Where the mesoderm layer provides an increase to the body's skeletal elements, such as relating to the cartilage or bone. The term "meso" means middle, infusion originated from the Greek, signifying that mesenchymal cells are able to range and travel in early embryonic growth among the ectodermal and endodermal layers. This mechanism helps with space-filling thus, key for repairing wounds in adult organisms that have to do with mesenchymal cells in the dermis (skin), bone, or muscle.<ref>{{cite journal | vauthors = Caplan AI | title = Mesenchymal stem cells | journal = Journal of Orthopaedic Research | volume = 9 | issue = 5 | pages = 641–650 | date = September 1991 | pmid = 1870029 | doi = 10.1002/jor.1100090504 | s2cid = 22606668 | doi-access = free }}</ref>
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[[Image:Stem cell division and differentiation.svg|thumb|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, 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
There are three known accessible sources of [[autologous]] adult stem cells in humans:
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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>
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>
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Adult stem cells have limitations with their potency; unlike [[embryonic stem cell]]s (ESCs), they are not able to differentiate into cells from all three [[germ layers]]. As such, they are deemed [[cell potency|multipotent]].
However, [[reprogramming]] allows for the creation of pluripotent cells, [[induced pluripotent stem cell]]s (iPSCs), from adult cells. These are not adult stem cells, but somatic 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.<ref name="Economist2007_11_22">{{cite news|title=Making human embryonic stem cells|newspaper=The Economist|url=http://www.economist.com/science/displaystory.cfm?story_id=10170972|date=2007-11-22}}</ref><ref>{{cite web|url=https://www.npr.org/templates/story/story.php?storyId=16466265|publisher=[[National Public Radio]]|title=Skin Cells Can Become Embryonic Stem Cells| last1 = Brand | first1 = Madeleine | last2 = Palca | first2 = Joe | last3 = Cohen | first3 = Alex | name-list-style = vanc |date=2007-11-20}}</ref><ref>{{cite web|url=https://www.pbs.org/newshour/bb/science/july-dec07/stemcells_11-20.html|title=Breakthrough Set to Radically Change Stem Cell Debate|publisher=[[News Hour with Jim Lehrer]]|date=2007-11-20|access-date=2017-09-15|archive-date=2014-01-22|archive-url=https://web.archive.org/web/20140122092539/http://www.pbs.org/newshour/bb/science/july-dec07/stemcells_11-20.html|url-status=dead}}</ref> The first demonstration of induced pluripotent stem cells was conducted by [[Shinya Yamanaka]] and his colleagues at [[Kyoto University]].<ref name = "overview">{{cite journal | vauthors = Kimbrel EA, Lanza R | title = Pluripotent stem cells: the last 10 years | journal = Regenerative Medicine | volume = 11 | issue = 8 | pages = 831–847 | date = December 2016 | pmid = 27908220 | doi = 10.2217/rme-2016-0117 | doi-access = free }}</ref> They used the transcription factors [[Oct-4|Oct3/4]], [[Sox2]], [[c-Myc]], and [[Klf4]] to reprogram mouse fibroblast cells into pluripotent cells.<ref name="Economist2007_11_22"/><ref name= "og Yak">{{cite journal | vauthors = Takahashi K, Yamanaka S | title = Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors | journal = Cell | volume = 126 | issue = 4 | pages = 663–676 | date = August 2006 | pmid = 16904174 | doi = 10.1016/j.cell.2006.07.024 | hdl = 2433/159777 | s2cid = 1565219 | hdl-access = free }}</ref> Subsequent work used these factors to induce pluripotency in human fibroblast cells.<ref name= "2007 Yak">{{cite journal | vauthors = Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S | title = Induction of pluripotent stem cells from adult human fibroblasts by defined factors | journal = Cell | volume = 131 | issue = 5 | pages = 861–872 | date = November 2007 | pmid = 18035408 | doi = 10.1016/j.cell.2007.11.019 | hdl = 2433/49782 | s2cid = 8531539 | hdl-access = free }}</ref> [[Junying Yu]], [[James Thomson (cell biologist)|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]].<ref name="Economist2007_11_22"/><ref name = "wisconsin">{{cite journal | vauthors = Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA | title = Induced pluripotent stem cell lines derived from human somatic cells | journal = Science | volume = 318 | issue = 5858 | pages = 1917–1920 | date = December 2007 | pmid = 18029452 | doi = 10.1126/science.1151526 | bibcode = 2007Sci...318.1917Y | s2cid = 86129154 }}</ref> However, they were able to replicate [[Yamanaka]]'s finding that inducing pluripotency in human cells was possible.
Induced pluripotent stem cells differ from embryonic stem cells. They share many similar properties, such as [[pluripotency]] and differentiation potential, the expression of [[pluripotency]] genes, [[epigenetic]] patterns, [[embryoid body]] and [[teratoma]] formation, and viable [[chimera (genetics)|chimera]] formation,<ref name="overview" /><ref name = "og Yak" /> but there are many differences within these properties. The chromatin of iPSCs appears to be more "closed" or methylated than that of ESCs.<ref name="overview" /><ref name = "og Yak" /> Similarly, the gene expression pattern between ESCs and iPSCs, or even iPSCs sourced from different origins.<ref name="overview" /> There are thus questions about the "completeness" of [[reprogramming]] and the somatic memory of induced pluripotent stem cells. Despite this, inducing somatic cells to be pluripotent appears to be viable.
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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.<ref>"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." {{cite news|url=https://www.telegraph.co.uk/science/science-news/3314696/Dolly-creator-Prof-Ian-Wilmut-shuns-cloning.html|archive-url=https://web.archive.org/web/20090730031336/http://www.telegraph.co.uk/science/science-news/3314696/Dolly-creator-Prof-Ian-Wilmut-shuns-cloning.html|archive-date=2009-07-30|title=Dolly creator Prof Ian Wilmut shuns cloning| last = Highfield | first = Roger | name-list-style = vanc |date=2007-11-16|newspaper=[[The Daily Telegraph|The Telegraph]] | location=London}}</ref>
*{{lay source |template=cite news |date=2010-07-01 |title=Frozen blood a source of stem cells, study finds |url=http://www.newsdaily.com/stories/tre6604si-us-stemcells-frozen |archive-url=https://web.archive.org/web/20100703175036/http://www.newsdaily.com/stories/tre6604si-us-stemcells-frozen/ |archive-date=2010-07-03 |work=NewsDaily |agency=Reuters}}</ref> Patient specific stem cells allow for the screening for side effects before drug treatment, as well as the reduced risk of transplantation rejection.<ref name= "R&D" /> Despite their current limited use therapeutically, iPSCs hold great potential for future use in medical treatment and research.
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{{Main|Stem cell therapy}}
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 because it has proven to be effective in clinical trials.<ref name="Why Perform a Stem Cell Transplant">
For over 90 years, [[hematopoietic stem cell transplantation]] (HSCT) has been used to treat people with conditions such as [[leukaemia]] and [[lymphoma]]; this is the only widely practiced form of stem-cell therapy.<ref name="Why Perform a Stem Cell Transplant"/><ref name="NCI2">
=== Advantages ===
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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.<ref>{{
Some stem cells form tumors after transplantation;<ref name = "usn2009">{{cite news|first=Bernadine |last=Healy
Ethical concerns are also raised about the practice of using or researching embryonic stem cells. Harvesting cells from the blastocyst results in the death of the blastocyst. The concern is whether or not the blastocyst should be considered as a human life.<ref>{{cite journal |title=Ethical Issues in Stem Cell Research |last1=Lo |first1=Bernard |last2=Parham |first2=Lindsay |journal=Endocrine Reviews |publisher=NIH |date=May 2009 |volume=30 |issue=3 |pages=204–213 |doi=10.1210/er.2008-0031 |pmid=19366754 |pmc=2726839 }}</ref> The debate on this issue is mainly a philosophical one, not a scientific one.
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{{Further|Consumer Watchdog vs. Wisconsin Alumni Research Foundation}}
Some of the fundamental [[patent]]s 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 Thomson (cell biologist)|James A. Thomson]]. WARF does not enforce these patents against academic scientists, but does enforce them against companies.<ref name = "stemcellPatent">
In 2006, a request for the [[US Patent and Trademark Office]] (USPTO) to re-examine the three patents was filed by the
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.<ref>
===
[[File:Stem cell treatments.svg|thumb|upright=1.5|Diseases and conditions where stem cell treatment is being investigated]]
Diseases and conditions where stem cell treatment is being investigated include:
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* [[Alzheimer's disease]]<ref name="nih" />
* [[Respiratory disease]]<ref>{{cite journal |last1=Hynds |first1=R |title=Exploiting the potential of lung stem cells to develop pro-regenerative therapies |journal=Biology Open |date=2022 |volume=11 |issue=10 |doi=10.1242/bio.059423 |pmid=36239242 |pmc=9581519 |doi-access=free }}</ref>
* [[Osteoarthritis]]<ref name="nih">
* [[Stroke]] and [[traumatic brain injury]] repair<ref name=Steinberg2000>{{cite news |last1=Steinberg |first1=Douglas |title=Stem Cells Tapped to Replenish Organs |url=https://www.the-scientist.com/research/stem-cells-tapped-to-replenish-organs-55310 |work=The Scientist Magazine |date=26 November 2000 }}</ref>
* [[Learning disability]] due to [[congenital disorder]]<ref>
* [[Spinal cord injury]] repair<ref>{{cite journal | vauthors = Kang KS, Kim SW, Oh YH, Yu JW, Kim KY, Park HK, Song CH, Han H | title = 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 | journal = Cytotherapy | volume = 7 | issue = 4 | pages = 368–373 | year = 2005 | pmid = 16162459 | doi = 10.1080/14653240500238160 | s2cid = 33471639 }}</ref>
* [[Heart infarction]]<ref>{{cite journal | vauthors = Strauer BE, Schannwell CM, Brehm M | title = Therapeutic potentials of stem cells in cardiac diseases | journal = Minerva Cardioangiologica | volume = 57 | issue = 2 | pages = 249–267 | date = April 2009 | pmid = 19274033 }}</ref>
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* [[Crohn's disease]]<ref>{{cite journal |last1=Anderson |first1=Querida |title=Osiris Trumpets Its Adult Stem Cell Product |journal=Genetic Engineering and Biotechnology News |date=15 June 2008 |volume=28 |issue=12 |url=https://www.genengnews.com/magazine/94/osiris-trumpets-its-adult-stem-cell-product/ }}</ref>
* [[Wound healing]]<ref>{{cite journal |last1=Gurtner |first1=Geoffrey C. |last2=Callaghan |first2=Matthew J. |last3=Longaker |first3=Michael T. |title=Progress and Potential for Regenerative Medicine |journal=Annual Review of Medicine |date=February 2007 |volume=58 |issue=1 |pages=299–312 |doi=10.1146/annurev.med.58.082405.095329 |pmid=17076602 }}</ref>
* [[Male infertility]] due to absence of spermatogonial stem cells.<ref>{{cite book |vauthors=Hanna V, Gassei K, Orwig KE | chapter = Stem Cell Therapies for Male Infertility: Where Are We Now and Where Are We Going? | veditors = Carrell D, Schlegel P, Racowsky C, Gianaroli L | title = Biennial Review of Infertility | pages = 17–39 | year = 2015 | publisher = Springer | doi = 10.1007/978-3-319-17849-3_3 | isbn = 978-3-319-17849-3 }} Bone marrow transplantation is, as of 2009, the only established use of stem cells.</ref> In recent studies, scientists have found a way to solve this problem by reprogramming a cell and turning it into a spermatozoon. Other studies have proven the restoration of spermatogenesis by introducing human iPSC cells in mice testicles. This could mean the end of [[azoospermia]].<ref>{{cite journal | vauthors = Valli H, Phillips BT, Shetty G, Byrne JA, Clark AT, Meistrich ML, Orwig KE | title = Germline stem cells: toward the regeneration of spermatogenesis | journal = Fertility and Sterility | volume = 101 | issue = 1 | pages = 3–13 | date = January 2014 | pmid = 24314923 | pmc = 3880407 | doi = 10.1016/j.fertnstert.2013.10.052 }}</ref>
* [[Female infertility]]: oocytes made from embryonic stem cells. Scientists have found the ovarian stem cells, a rare type of cells (0.014%) found in the ovary. They could be used as a treatment not only for infertility, but also for premature ovarian insufficiency (POI).<ref>{{cite journal | vauthors = White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL | title = Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women | journal = Nature Medicine | volume = 18 | issue = 3 | pages = 413–421 | date = February 2012 | pmid = 22366948 | pmc = 3296965 | doi = 10.1038/nm.2669 }}</ref> New research posted in Science Direct suggests that ovarian follicles could be triggered to grow in the ovarian environment by using stem cells present in [[bone marrow]]. This study was conducted by infusing human bone marrow stem cells into immune-deficient mice to imrpove fertilization.<ref>{{Cite journal |last1=Herraiz |first1=Sonia |last2=Buigues |first2=Anna |last3=Díaz-García |first3=César |last4=Romeu |first4=Mónica |last5=Martínez |first5=Susana |last6=Gómez-Seguí |first6=Inés |last7=Simón |first7=Carlos |last8=Hsueh |first8=Aaron J. |last9=Pellicer |first9=Antonio |date=May 2018 |title=Fertility rescue and ovarian follicle growth promotion by bone marrow stem cell infusion |url=https://linkinghub.elsevier.com/retrieve/pii/S0015028218300049 |journal=Fertility and Sterility |volume=109 |issue=5 |pages=908–918.e2 |doi=10.1016/j.fertnstert.2018.01.004 |pmid=29576341 |issn=0015-0282}}</ref> Another study conducted using mice with damanged ovarian function from [[Chemotherapy|chemothearpy]] found that [[in vivo]] thearpy with bone marrow stem cells can heal the damaged ovaries. <ref>{{Cite journal |last1=Badawy |first1=Ahmed |last2=Sobh |first2=Mohamed A. |last3=Ahdy |first3=Mohamed |last4=Abdelhafez |first4=Mohamed Sayed |date=2017-06-15 |title=Bone marrow mesenchymal stem cell repair of cyclophosphamide-induced ovarian insufficiency in a mouse model |journal=International Journal of Women's Health |language=English |volume=9 |pages=441–447 |doi=10.2147/IJWH.S134074 |doi-access=free |pmc=5479293 |pmid=28670143}}</ref> Both of these studies are [[Proof of concept|proof-of-concept]] and need to be furthered tested, but they have the possibility improve fertility for individuals who have POI from chemothearpy treatment.
* Critical Limb Ischemia<ref>{{Cite journal |last1=Liew |first1=Aaron |last2=O'Brien |first2=Timothy |date=2012-07-30 |title=Therapeutic potential for mesenchymal stem cell transplantation in critical limb ischemia |journal=Stem Cell Research & Therapy |volume=3 |issue=4 |pages=28 |doi=10.1186/scrt119 |issn=1757-6512 |pmc=3580466 |pmid=22846185 |doi-access=free }}</ref>
=== Production ===
Research is underway to develop various sources for stem cells
=== Organoids ===
Research is attempting to generating [[organoid]]s using stem cells, which would allow for further understanding of human development, [[organogenesis]], and modeling of human diseases.<ref name="pmid25033469">{{cite journal | vauthors = Ader M, Tanaka EM | title = Modeling human development in 3D culture | journal = Current Opinion in Cell Biology | volume = 31 | pages = 23–28 | date = December 2014 | pmid = 25033469 | doi = 10.1016/j.ceb.2014.06.013 }}</ref> Engineered ‘synthetic organizer’ (SO) cells can instruct stem cells to grow into specific tissues and organs. The program used native and synthetic [[Cell adhesion molecules|cell adhesion protein molecules]] (CAMs) that help make cells sticky. The organizer cells self-assembled around mouse ESCs. These cells were engineered to produce [[morphogens]] (signaling molecules) that direct cellular development based on their concentration. Delivered morphogens disperse, leaving higher concentrations closer to the source and lower concentrations further away. These gradients signal cells' ultimate roles, such as nerve, skin cell, or connective tissue. The engineered organizer cells were also fitted with a chemical switch that enabled the researchers to turn the delivery of cellular instructions on and off, as well as a ‘suicide switch’ for eliminating the cells when needed. SOs carry spatial and biochemical information, allowing considerable discretion in organoid formation.<ref>{{Cite web |last=McClure |first=Paul |date=2024-12-27 |title=Stem cells 'instructed' to form specific tissues and organs |url=https://newatlas.com/medical/stem-cells-organizing-cell-morphogens/ |access-date=2024-12-28 |website=New Atlas |language=en-US}}</ref>
=== Risks ===
[[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.<ref name="stem2012">{{cite journal |last1=Greenhough |first1=Sebastian |last2=Hay |first2=David C. |title=Stem Cell-Based Toxicity Screening: Recent Advances in Hepatocyte Generation |journal=Pharmaceutical Medicine |date=April 2012 |volume=26 |issue=2 |pages=85–89 |doi=10.1007/BF03256896 |s2cid=15893493 }}</ref>
===
In August 2021, researchers in the [[Princess Margaret Cancer Centre]] at the [[University Health Network]] published their discovery of a dormancy mechanism in key stem cells which could help develop cancer treatments in the future.<ref>{{cite journal |last1=García-Prat |first1=Laura |last2=Kaufmann |first2=Kerstin B. |last3=Schneiter |first3=Florin |last4=Voisin |first4=Veronique |last5=Murison |first5=Alex |last6=Chen |first6=Jocelyn |last7=Chan-Seng-Yue |first7=Michelle |last8=Gan |first8=Olga I. |last9=McLeod |first9=Jessica L. |last10=Smith |first10=Sabrina A. |last11=Shoong |first11=Michelle C. |last12=Parris |first12=Darrien |last13=Pan |first13=Kristele |last14=Zeng |first14=Andy G.X. |last15=Krivdova |first15=Gabriela |last16=Gupta |first16=Kinam |last17=Takayanagi |first17=Shin-Ichiro |last18=Wagenblast |first18=Elvin |last19=Wang |first19=Weijia |last20=Lupien |first20=Mathieu |last21=Schroeder |first21=Timm |last22=Xie |first22=Stephanie Z. |last23=Dick |first23=John E. |title=TFEB-mediated endolysosomal activity controls human hematopoietic stem cell fate |journal=Cell Stem Cell |date=August 2021 |volume=28 |issue=10 |pages=1838–1850.e10 |doi=10.1016/j.stem.2021.07.003 |pmid=34343492 |s2cid=236915618 |doi-access=free |hdl=20.500.11850/510219 |hdl-access=free }}</ref>
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{{Commons category|Stem cells}}
{{Library resources box |by=no |onlinebooks=no |others=yes lcheading=Stem cells}}
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{{Wound healing}}
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