Examine individual changes

'{{About|the cell type|the medical therapy|Stem cell treatment}} {{Infobox Anatomy | Name = Stem cell | Latin = Cellula praecursoria | GraySubject = | GrayPage = | Image = MSC high magnification.jpg | Caption = Adult stem cell displaying typical ultrastructural characteristics. | Image2 = | Caption2 = | Precursor = | System = | Artery = | Vein = | Nerve = | Lymph = | MeshName = | MeshNumber = | Code = [[Terminologia Histologica|TH]] H2.00.01.0.00001 }} '''Stem cells''' are [[Cellular differentiation|undifferentiated]] [[cell (biology)|biological cells]] that can [[Cellular differentiation|differentiate]] into specialized cells and can [[cell division|divide]] (through [[mitosis]]) to produce more stem cells. They are found in multicellular [[organisms]]. In [[mammal]]s, there are two broad types of stem cells: [[embryonic stem cell]]s, which are isolated from the [[inner cell mass]] of [[blastocyst]]s, and [[adult stem cell]]s, which are found in various tissues. In [[adult]] organisms, stem cells and [[progenitor cell]]s act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cells—ectoderm, endoderm and mesoderm (see [[induced pluripotent stem cells]])—but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues. There are three accessible sources of [[autologous]] adult stem cells in humans: # Bone marrow, which requires extraction by ''harvesting'', that is, drilling into bone (typically the [[femur]] or [[iliac crest]]), # Adipose tissue (lipid cells), which requires extraction by liposuction, and # Blood, which requires extraction through [[apheresis]], wherein blood is drawn from the donor (similar to a blood donation), and passed through a machine that extracts the stem cells and returns other portions of the blood to the donor. Stem cells can also be taken from [[umbilical cord blood]] just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank his or her own blood for elective surgical procedures. Adult stem cells are frequently used in medical therapies, for example in [[Hematopoietic stem cell transplantation|bone marrow transplantation]]. Stem cells can now be [[Cell culture|artificially grown]] and transformed (differentiated) into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves. Embryonic [[cell line]]s and [[autologous]] embryonic stem cells generated through [[therapeutic cloning]] have also been proposed as promising candidates for future therapies.<ref>{{cite journal | author=Tuch BE | title=Stem cells—a clinical update | journal=[[Australian Family Physician]] | volume=35 | issue=9 | pages=719–21 | year=2006 | pmid=16969445}}</ref> Research into stem cells grew out of findings by [[Ernest McCulloch|Ernest A. McCulloch]] and [[James Till|James E. Till]] at the [[University of Toronto]] in the 1960s.<ref>{{cite journal | authors = 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 = 452–4 | year = 1963 | pmid = 13970094 | doi=10.1038/197452a0 | bibcode = 1963Natur.197..452B }}</ref><ref>{{cite journal | authors = 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 = 327–36 | year = 1963 | pmid = 14086156 | doi = 10.1002/jcp.1030620313}}</ref> ==Properties== The classical definition of a stem cell requires that it possess two properties: *''Self-renewal'': the ability to go through numerous [[cell cycle|cycles]] of [[cell division]] while maintaining the undifferentiated state. *''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 feed back mechanism. ===Self-renewal=== Two mechanisms exist to ensure that a stem cell population is maintained: # [[Asymmetric cell division|Obligatory asymmetric replication]]: a stem cell divides into one mother cell that is identical to the original stem cell, and another daughter cell that is differentiated. # Stochastic differentiation: when one stem cell develops into two differentiated daughter cells, another stem cell undergoes [[mitosis]] and produces two stem cells identical to the original. ===Potency definition=== {{Main|Cell potency}} [[Image:Stem cells diagram.png|400px|thumb|right|Pluripotent, embryonic stem cells originate as inner cell mass (ICM) cells within a blastocyst. These stem cells can become any tissue in the body, excluding a placenta. Only cells from an earlier stage of the embryo, known as the [[morula]], are totipotent, able to become all tissues in the body and the extraembryonic placenta.]] [[Image:Human embryonic stem cells.png|thumb|250px|Human [[embryo]]nic stem cells <br /> A: Stem cell colonies that are not yet differentiated. <br /> B: [[Nerve]] cells, an example of a [[cell type]] after differentiation.]] ''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 |editor=Nikolaus Knoepffler, Dagmar Schipanski, and Stefan Lorenz Sorgner |page=28 |chapter=The Potential of Stem Cells: An Inventory |author=Schöler, Hans R. |publisher=Ashgate Publishing|year=2007 |isbn=978-0-7546-5755-2}}</ref> *[[Totipotency|Totipotent]] (a.k.a. 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 fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent.<ref>{{cite journal |title=Totipotency, pluripotency and nuclear reprogramming |authors=Mitalipov S, Wolf D |journal=Adv. Biochem. Eng. Biotechnol. |year=2009 |volume=114 |pages=185–99 |pmid=19343304 |pmc=2752493 |doi=10.1007/10_2008_45 |series=Advances in Biochemical Engineering/Biotechnology |isbn=978-3-540-88805-5 |bibcode=2009esc..book..185M }}</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 |author=Ulloa-Montoya F, Verfaillie CM, Hu WS |title=Culture systems for pluripotent stem cells |journal=J Biosci Bioeng. |volume=100 |issue=1 |pages=12–27 |year=2005 |pmid=16233846 |doi=10.1263/jbb.100.12 }}</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/> *[[Oligopotency|Oligopotent]] stem cells can differentiate into only a few cell types, such as lymphoid or myeloid stem cells.<ref name=Schoeler/> *[[Unipotency|Unipotent]] cells can produce only one cell type, their own,<ref name=Schoeler/> but have the property of self-renewal, which distinguishes them from non-stem cells (e.g. [[progenitor cell]]s, muscle stem cells). ===Identification=== In practice, stem cells are identified by whether they can regenerate tissue. For example, the defining test for bone marrow or [[hematopoietic stem cell]]s (HSCs) is the ability to transplant the cells and save an individual without HSCs. This demonstrates that the cells can produce new blood cells over a long term. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew. Properties of stem cells can be illustrated ''[[in vitro]]'', using methods such as [[clonogenic assay]]s, in which single cells are assessed for their ability to differentiate and self-renew.<ref>{{cite journal | author = Friedenstein AJ, Deriglasova UF, Kulagina NN, Panasuk AF, Rudakowa SF, Luria EA, Ruadkow IA | title = Precursors for fibroblasts in different populations of hematopoietic cells as detected by the ''in vitro'' colony assay method | journal = [[Experimental Hematology]] | issn = 0301-472X | volume = 2 | issue = 2 | pages = 83–92 | year = 1974 | pmid = 4455512 }}</ref><ref> {{cite journal | author = Friedenstein AJ, Gorskaja JF, Kulagina NN | title = Fibroblast precursors in normal and irradiated mouse hematopoietic organs | journal = [[Experimental Hematology]] | volume = 4 | issue = 5 | pages = 267–74 | year = 1976 | pmid = 976387 }}</ref> Stem cells can also be isolated by their possession of a distinctive set of cell surface markers. However, ''in vitro'' culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar manner ''[[in vivo]]''. There is considerable debate as to whether some proposed adult cell populations are truly stem cells. ==Embryonic== {{Main|Embryonic stem cell}} Embryonic stem (ES) cells are stem cells derived from the [[inner cell mass]] of a [[blastocyst]], an early-stage [[embryo]].<ref>{{cite journal |author=Thomson et. al |title=Blastocysts Embryonic Stem Cell Lines Derived from Human |journal=Science |volume=282 |issue=5391 |pages=1145–1147 |year=1998 |pmid= 9804556|doi=10.1126/science.282.5391.1145 |last2=Itskovitz-Eldor |first2=J |last3=Shapiro |first3=SS |last4=Waknitz |first4=MA |last5=Swiergiel |first5=JJ |last6=Marshall |first6=VS |last7=Jones |first7=JM|bibcode=1998Sci...282.1145T }}</ref> Human [[embryo]]s reach the [[blastocyst]] stage 4–5 days post [[Human fertilization|fertilization]], at which time they consist of 50–150 cells. ES cells are [[pluripotent]] and give rise during development to all derivatives of the three primary [[germ 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 extra-embryonic membranes or the [[placenta]]. Nearly all research to date has made use of mouse embryonic stem cells (mES) or human embryonic stem cells (hES). 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). Human ES cells are grown on a feeder layer of mouse embryonic [[fibroblasts]] (MEFs) and require the presence of basic fibroblast growth factor (bFGF or FGF-2).<ref> {{cite web |url=http://stemcells.nih.gov/research/NIHresearch/scunit/culture.asp |archiveurl=http://web.archive.org/web/20100106111652/http://stemcells.nih.gov/research/NIHresearch/scunit/culture.asp |archivedate=2010-01-06 |title=Culture of Human Embryonic Stem Cells (hESC) |publisher=National Institutes of Health |accessdate=2010-03-07 }}</ref> Without optimal culture conditions or genetic manipulation,<ref> {{cite journal |author=Chambers I |title=Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells |journal=Cell |volume=113 |issue=5 |pages=643–55 |year=2003 |pmid=12787505 |doi=10.1016/S0092-8674(03)00392-1 |author2=Colby D |author3=Robertson M |last4=Nichols |first4=Jennifer |last5=Lee |first5=Sonia |last6=Tweedie |first6=Susan |last7=Smith |first7=Austin }}</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]], [[Nanog]], and [[Sox2]] form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.<ref> {{cite journal |author=Boyer LA |title=Core transcriptional regulatory circuitry in human embryonic stem cells |journal=Cell |volume=122 |issue=6 |pages=947–56 |year=2005 |pmid=16153702 |pmc=3006442 |doi=10.1016/j.cell.2005.08.020 |author2=Lee TI |author3=Cole MF |last4=Johnstone |first4=Sarah E. |last5=Levine |first5=Stuart S. |last6=Zucker |first6=Jacob P. |last7=Guenther |first7=Matthew G. |last8=Kumar |first8=Roshan M. |last9=Murray |first9=Heather L. |last10=Jenner |first10=Richard G. |last11=Gifford |first11=David K. |last12=Melton |first12=Douglas A. |last13=Jaenisch |first13=Rudolf |last14=Young |first14=Richard A. |display-authors=8 }}</ref> The cell surface antigens most commonly used to identify hES cells are the glycolipids [[stage specific embryonic antigen 3]] and 4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.<ref> {{cite journal |title=Characterization of human embryonic stem cell lines by the International Stem Cell Initiative |journal=Nat. Biotechnol |volume=25 |issue=7 |pages=803–16 |year=2007 |pmid=17572666 |doi=10.1038/nbt1318 |last4=Amit |first4=Michal |last5=Andrews |first5=Peter W |last6=Beighton |first6=Gemma |last7=Bello |first7=Paul A |last8=Benvenisty |first8=Nissim |last9=Berry |first9=Lorraine S |last10=Bevan |first10=Simon |last11=Blum |first11=Barak |last12=Brooking |first12=Justin |last13=Chen |first13=Kevin G |last14=Choo |first14=Andre B H |last15=Churchill |first15=Gary A |last16=Corbel |first16=Marie |last17=Damjanov |first17=Ivan |last18=Draper |first18=Jon S |last19=Dvorak |first19=Petr |last20=Emanuelsson |first20=Katarina |last21=Fleck |first21=Roland A |last22=Ford |first22=Angela |last23=Gertow |first23=Karin |last24=Gertsenstein |first24=Marina |last25=Gokhale |first25=Paul J |last26=Hamilton |first26=Rebecca S |last27=Hampl |first27=Ales |last28=Healy |first28=Lyn E |last29=Hovatta |first29=Outi |last30=Hyllner |first30=Johan |display-authors=8 |last1 = Adewumi|first1 = O.}}</ref> There are currently no approved treatments using embryonic stem cells. The first human trial was approved by the US Food and Drug Administration in January 2009.<ref> {{cite journal | author = Ron Winslow | title = First Embryonic Stem-Cell Trial Gets Approval from the FDA | series = 23 | journal = The Wall Street Journal |url=http://online.wsj.com/article/SB123268485825709415.html | volume = January 2009 | year = 2009 }}</ref> However, the human trial was not initiated until October 13, 2010 in Atlanta for spinal injury victims. On November 14, 2011 the company conducting the trial announced that it will discontinue further development of its stem cell programs.<ref> {{cite web |url=http://www.sciencedebate.com/science-blog/embryonic-stem-cell-therapy-risk-geron-ends-clinical-trial |publisher=ScienceDebate.com |title=Embryonic Stem Cell Therapy At Risk? Geron Ends Clinical Trial |accessdate=2011-12-11 }}</ref> ES cells, being pluripotent cells, require specific signals for correct differentiation—if injected directly into another body, ES cells will differentiate into many different types of cells, causing a [[teratoma]]. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face.<ref> {{cite journal |author=Wu DC, Boyd AS, Wood KJ |title=Embryonic stem cell transplantation: potential applicability in cell replacement therapy and regenerative medicine |journal=Front Biosci |volume=12 |issue=8–12|pages=4525–35 |year=2007 |pmid=17485394 |doi=10.2741/2407 }}</ref> Many nations currently have [[moratorium (law)|moratoria]] on either ES cell research or the production of new ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for [[regenerative medicine]] and tissue replacement after injury or disease. <gallery> Image:Mouse embryonic stem cells.jpg | [[Mus musculus|Mouse]] [[Mammalian embryogenesis|embryo]]nic stem cells with fluorescent marker Image:Human embryonic stem cell colony phase.jpg | Human embryonic stem cell colony on mouse embryonic fibroblast feeder layer </gallery> ==Fetal== The primitive stem cells located in the organs of fetuses are referred to as fetal stem cells.<ref name="isbn981-256-126-9"> {{cite book |editor=Ariff Bongso; Eng Hin Lee |title=Stem Cells: From Benchtop to Bedside |chapter=Stem cells: their definition, classification and sources |publisher=World Scientific |year=2005 |page=5 |isbn=981-256-126-9 |oclc=443407924 }}</ref> There are two types of fetal stem cells: # Fetal proper stem cells come from the tissue of the fetus proper, and are generally obtained after an abortion. These stem cells are not immortal but have a high level of division and are multipotent. # Extraembryonic fetal stem cells come from extraembryonic membranes, and are generally not distinguished from adult stem cells. These stem cells are acquired after birth, they are not immortal but have a high level of cell division, and are pluripotent.<ref>Moore, K.L., T.V.N. Persaud, and A.G. Torchia. Before We Are Born: Essentials of Embryology and Birth Defects. Philadelphia, PA: Saunders, Elsevier. 2013. Print</ref> ==Adult== {{Main|Adult stem cell}} [[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]] (from Greek Σωματικóς, "of the body") stem cells, are stem cells which maintain and repair the tissue in which they are found.<ref>"Stem Cells" Mayo Clinic. Mayo foundation for medical education and research n.d Web. March 23, 2013</ref> They can be found in children, as well as adults.<ref>{{cite journal |author=Jiang Y |title=Pluripotency of mesenchymal stem cells derived from adult marrow |journal=Nature |volume=418 |issue=6893 |pages=41–9 |year=2002 |pmid=12077603 |doi=10.1038/nature00870 |author2=Jahagirdar BN |author3=Reinhardt RL |last4=Schwartz |first4=Robert E. |last5=Keene |first5=C. Dirk |last6=Ortiz-Gonzalez |first6=Xilma R. |last7=Reyes |first7=Morayma |last8=Lenvik |first8=Todd |last9=Lund |first9=Troy|last10=Blackstad |first10=Mark |last11=Du |first11=Jingbo |last12=Aldrich |first12=Sara |last13=Lisberg |first13=Aaron |last14=Low |first14=Walter C. |last15=Largaespada |first15=David A. |last16=Verfaillie |first16=Catherine M. |display-authors=8 }}</ref> 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 |author=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=860–7 |year=2007 |pmid=17344915 |doi=10.1038/sj.leu.2404630}}</ref> Bone marrow is a rich source of adult stem cells,<ref>{{cite journal| author = Narasipura SD | title = P-Selectin coated microtube for enrichment of CD34+ hematopoietic stem and progenitor cells from human bone marrow | journal = Clin Chem | year = 2008 | pmid=18024531 | doi=10.1373/clinchem.2007.089896 | volume=54 | issue=1 | pages=77–85| last2 = Wojciechowski| first2 = J. C.| last3 = Charles| first3 = N.| last4 = Liesveld| first4 = J. L.| last5 = King| first5 = M. R.}}</ref> which have been used in treating several conditions including spinal cord injury,<ref>{{cite journal|url=http://www.omicsonline.org/2157-7633/2157-7633-1-110.php | author = William JB | title = Functional Recovery of Spinal Cord Injury Following Application of Intralesional Bone Marrow Mononuclear Cells Embedded in Polymer Scaffold – Two Year Follow-up in a Canine | journal = Journal of Stem Cell Research & Therapy| year = 2011|doi=10.4172/2157-7633.1000110|last2=Prabakaran|first2=Rajamanickam|last3=Ayyappan|first3=Subbu|volume=01|issue=3}}</ref> liver cirrhosis,<ref>{{cite journal| author = Terai S | title = Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy | journal = Stem Cells | year = 2006 | pmid=16778155 | doi=10.1634/stemcells.2005-0542 | volume=24 | issue=10 | pages=2292–8| last2 = Ishikawa| first2 = Tsuyoshi| last3 = Omori| first3 = Kaoru| last4 = Aoyama| first4 = Koji| last5 = Marumoto| first5 = Yoshio| last6 = Urata| first6 = Yohei| last7 = Yokoyama| first7 = Yuichirou| last8 = Uchida| first8 = Koichi| last9 = Yamasaki| first9 = Takahiro| last10 = Fujii | first10 = Yasuhiko | last11 = Okita | first11 = Kiwamu | last12 = Sakaida | first12 = Isao | display-authors = 8 }}</ref> chronic limb ischemia <ref>{{cite journal|url=http://www.ncbi.nlm.nih.gov/pubmed?term=Application%20of%20autologous%20bone%20marrow%20mononuclear%20cells%20in%20six%20patients%20with%20advanced%20chronic%20critical%20limb%20ischemia%20as%20a%20result%20of%20diabetes%3A%20our%20experience | author = Subrammaniyan R | 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 | year = 2011 |doi=10.3109/14653249.2011.579961 |last2=Amalorpavanathan |first2=Joseph |last3=Shankar |first3=Rajendran |last4=Rajkumar |first4=Murugesan |last5=Baskar |first5=Subramani |last6=Manjunath |first6=Sadananda Rao |last7=Senthilkumar |first7=Rajappa |last8=Murugan |first8=Palanisamy |last9=Srinivasan |first9=Venkaba Rao | last10 = Abraham | first10 = Samuel |volume=13 |issue=8 |pages=993–9 |pmid=21671823| display-authors = 8 }}</ref> and endstage heart failure.<ref>{{cite journal|url=http://www.pubstemcell.com/monthly/003010700010.htm | author = Madhusankar N | title = Use of Bone Marrow derived Stem Cells in Patients with Cardiovascular Disorders | journal = Journal of Stem Cells and Regenerative Medicine }}</ref> The quantity of bone marrow stem cells declines with age and is greater in males than females during reproductive years.<ref>{{cite journal | author = Dedeepiya VD | 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 Res | year = 2012 | pmid = 22830032 | doi=10.1155/2012/787414 | volume=2012 | pmc=3398573 | page=787414 |last2=Rao |first2=Yegneswara Yellury |last3=Jayakrishnan |first3=Gosalakkal A. |last4=Parthiban |first4=Jutty K. B. C. |last5=Baskar |first5=Subramani |last6=Manjunath |first6=Sadananda Rao |last7=Senthilkumar |first7=Rajappa |last8=Abraham |first8=Samuel J. K.}}</ref> Much adult stem cell research to date has aimed to characterize their potency and self-renewal capabilities.<ref>{{cite journal | author = Gardner RL | title = Stem cells: potency, plasticity and public perception | journal = Journal of Anatomy | volume = 200 | issue = 3 | pages = 277–82 | year = 2002 | pmid = 12033732 | doi=10.1046/j.1469-7580.2002.00029.x | pmc = 1570679}}</ref> In mice, pluripotent stem cells are directly generated from adult fibroblast cultures. However, mice do not live long with stem cell organs.<ref name="Takahashi2006">{{cite journal |author=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=663–76 |year=2006 |pmid=16904174 |doi=10.1016/j.cell.2006.07.024}}</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 |author=Barrilleaux B, Phinney DG, Prockop DJ, O'Connor KC |title=Review: ex vivo engineering of living tissues with adult stem cells |journal=Tissue Eng |volume=12 |issue=11 |pages=3007–19 |year=2006 |pmid=17518617 |doi=10.1089/ten.2006.12.3007}}</ref><ref>{{cite journal |author=Gimble JM, Katz AJ, Bunnell BA |title=Adipose-derived stem cells for regenerative medicine |journal=Circ Res |volume=100 |issue=9 |pages=1249–60 |year=2007 |pmid=17495232 |doi=10.1161/01.RES.0000265074.83288.09}}</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}}</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 |accessdate=2008-06-12}}</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=http://www.hhs.gov/news/press/2004pres/20040714b.html |archiveurl=http://web.archive.org/web/20090109104735/http://www.hhs.gov/news/press/2004pres/20040714b.html |archivedate=2009-01-09 |publisher=US Department of Health and Human Services |title=Stem Cell FAQ |date=2004-07-14}}</ref> ==Amniotic== Multipotent stem cells are also found in [[amniotic fluid]]. These stem cells are very active, expand extensively without feeders and are not tumorigenic. [[Amniotic stem cells]] are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines.<ref> {{cite journal |author=P. De Coppi, G Barstch, Anthony Atala |title=Isolation of amniotic stem cell lines with potential for therapy |journal=Nature Biotechnology |volume=25 |issue=5 |pages=100–106 |year=2007 |pmid=17206138 |doi=10.1038/nbt1274 }}</ref> Amniotic stem cells are a topic of active research. Use of stem cells from [[amniotic fluid]] overcomes the ethical objections to using human embryos as a source of cells. [[Roman Catholic]] teaching forbids the use of embryonic stem cells in experimentation; accordingly, the [[Holy See|Vatican]] newspaper "[[Osservatore Romano]]" called amniotic stem cells "the future of medicine".<ref>{{cite web|url=http://www.catholicnewsagency.com/news/vatican_newspaper_calls_new_stem_cell_source_future_of_medicine/ |title=Vatican newspaper calls new stem cell source 'future of medicine' :: Catholic News Agency (CNA) |publisher=Catholic News Agency |date=2010-02-03 |accessdate=2010-03-14}}</ref> It is possible to collect amniotic stem cells for donors or for autologuous use: the first US amniotic stem cells bank <ref>{{cite news|url=http://www.reuters.com/article/pressRelease/idUS166682+22-Oct-2009+PRN20091022 |title=European Biotech Company Biocell Center Opens First U.S. Facility for Preservation of Amniotic Stem Cells in Medford, Massachusetts |publisher=Reuters |date=2009-10-22 |accessdate=2010-03-14}}</ref><ref>{{cite news|url=http://www.boston.com/business/ticker/2009/10/europes_biocell.html |title=Europe's Biocell Center opens Medford office – Daily Business Update |work=The Boston Globe |date=2009-10-22 |accessdate=2010-03-14}}</ref> was opened in 2009 in Medford, MA, by [[Biocell Center]] Corporation<ref>{{cite web|url=http://www.bostonherald.com/business/general/view/20091022the_ticker/ |title=The Ticker |publisher=BostonHerald.com |date=2009-10-22 |accessdate=2010-03-14}}</ref><ref>{{cite web|url= http://www.masshightech.com/stories/2009/10/19/daily59-Biocell-Center-opens-amniotic-stem-cell-bank-in-Medford.html |title=Biocell Center opens amniotic stem cell bank in Medford |work=Mass High Tech Business News|date=2009-10-23 |accessdate=2012-08-26}}</ref><ref>{{cite web|url=http://www.wbur.org/2009/10/22/stem-cell-bank |title=News » World’s First Amniotic Stem Cell Bank Opens In Medford |publisher=wbur.org |accessdate=2010-03-14}}</ref> and collaborates with various hospitals and universities all over the world.<ref>{{cite web|url=http://www.prnewswire.com/news-releases/biocell-center-corporation-partners-with-new-englands-largest-community-based-hospital-network-to-offer-a-unique-service-in-amniotic-fluid-stem-cell-preservation-86848157.html |title=Biocell Center Corporation Partners with New England's Largest Community-Based Hospital Network to Offer a Unique... – MEDFORD, Mass., March 8 /PRNewswire/ |location=Massachusetts |publisher=Prnewswire.com |accessdate=2010-03-14}}</ref> ==Cord blood== {{Main|Cord blood-derived multipotent stem cell}} A certain kind of [[cord blood-derived multipotent stem cell|cord blood stem cell]] (CB-SC) is multipotent and displays embryonic and [[hematopoietic]] characteristics. Phenotypic characterization demonstrates that (CB-SCs) display embryonic cell markers (e.g., [[transcription factors]] OCT-4 and [[Nanog]], stage-specific embryonic [[antigen]] [[Stage specific embryonic antigen 3|(SSEA)-3]], and SSEA-4) and [[leukocyte common antigen]] [[CD45]], but that they are negative for blood cell lineage markers (e.g., [[CD1a]], [[CD3 (immunology)|CD3]], [[CD4]], [[CD8]], [[CD11b]], [[CD11c]], [[CD13]], [[CD14]], [[CD19]], [[CD20]], [[CD34]], [[CD41]]a, [[CD41]]b, [[CD83]], [[CD90]], [[CD105]], and [[CD133]]).<ref name="Identification"> {{cite journal |author=Zhao, Yong; Wang, Honglan and Mazzone, Theodore |title=Identification of stem cells from human umbilical cord blood with embryonic and hematopoietic characteristics |journal=Exp Cell Res |url=http://www.tianhecell.com/uploads/ECRStemCell.pdf |volume=312 |issue=13 |pages=2454–2464 |date=Aug 1, 2006 |pmid=16716296 |doi=10.1016/j.yexcr.2006.04.008 }}</ref><ref name="Human modulated"> {{cite journal |author=Zhao, Yong; Lin, Brian; Darflinger, Robert; Zhang, Yongkang; Holterman, Mark J. and Skidgel, Randal A. |title=Human cord blood stem cell-modulated regulatory T lymphocytes reverse the autoimmune-caused type 1 diabetes in nonobese diabetic (NOD) mice |journal=PLoS ONE |url=http://www.tianhecell.com/uploads/PlosOne.pdf |volume=4 |issue=1 |pages=e4226 |date=January 19, 2009 |pmid=19156219 |pmc=2627485 |doi=10.1371/journal.pone.0004226 |editor1-last=Unutmaz |editor1-first=Derya |bibcode=2009PLoSO...4.4226Z |last2=Lin |last3=Darflinger |last4=Zhang |last5=Holterman |last6=Skidgel }}</ref> Additionally, CB-SCs display very low [[immunogenicity]] as indicated by expression of a very low level of [[major histocompatibility complex]] (MHC) antigens and failure to stimulate the proliferation of [[allogeneic]] [[lymphocytes]].<ref name="Identification" /><ref name="Immune"> {{cite journal |author=Zhao, Yong; Wang, Honglan and Mazzone, Theodore |title=Immune regulation of T lymphocyte by a newly characterized human umbilical cord blood stem cell |journal=Immunol Lett |url=http://www.tianhecell.com/uploads/ImmunologyLetters.pdf |volume=108 |issue=1 |pages=78–87 |year=2007 |pmid=17161871 |doi=10.1016/j.imlet.2006.10.007 }}</ref> They can give rise to three embryonic layer-derived cells in the presence of different [[inducer]]s.<ref name="Identification" /><ref name="Human journey"> {{cite journal |author=Yong Zhao, Theodore Mazzone |title=Human cord blood stem cells and the journey to a cure for type 1 diabetes |journal=Autoimmun Rev |url=http://www.tianhecell.com/uploads/AutoimmunityReviewsT1D.pdf |volume=10 |issue=2 |pages=103–107 |year=2010 |pmid=20728583 |doi=10.1016/j.autrev.2010.08.011 }}</ref> More specifically, CB-SCs tightly adhere to culture dishes with a large rounded [[morphology (biology)|morphology]] and are resistant to common detaching methods ([[trypsin]]/[[EDTA]]).<ref name="Identification" /><ref name="Immune" /><ref name="Human journey" /> CB-SCs are the active agent in [[stem cell educator]] therapy, which has therapeutic potential against [[autoimmune diseases]] like [[type 1 diabetes]] according to studies by Yong Zhao ''et al.''<ref name="Human modulated" /><ref name="New type"> {{cite journal |author=Zhao Y, Lin B, Dingeldein M, Guo C, Hwang D, Holterman MJ. |title=New type of human blood stem cell: a double-edged sword for the treatment of type 1 diabetes |journal=Transl Res. |url=http://www.tianhecell.com/uploads/TranslationalRes.pdf |volume=155 |issue=5 |pages=211–216 |year=2010 May |pmid=20403575 |doi=10.1016/j.trsl.2010.01.003 }}</ref><ref name="Reversal"> {{cite journal |author=Yong Zhao, Zhaoshun Jiang, Tingbao Zhao, Mingliang Ye, Chengjin Hu, Zhaohui Yin, Heng Li, Ye Zhang, Yalin Diao, Yunxiang Li, Yingjian Chen, Xiaoming Sun, Mary Beth Fisk, Randal Skidgel, Mark Holterman, Bellur Prabhakar, Theodore Mazzone |title=Reversal of type 1 diabetes via islet ß cell regeneration following immune modulation by cord blood-derived multipotent stem cells |journal=BMC Medicine 2012 |url=http://www.tianhecell.com/uploads/BMCMedicine.pdf |volume=10 |pages=1–11 |date=Jan 10, 2012 |pmid=22233865 |doi=10.1186/1741-7015-10-3 |pmc=3322343 }}</ref><ref name="immune balance"> {{cite journal |author=Yong Zhao |title=Stem cell educator therapy and induction of immune balance |journal=Curr Diab Rep |url=http://www.tianhecell.com/uploads/CurrentDiabetesReports.pdf |volume=12 |issue=5 |pages=517–523 |year=2012 Oct |pmid=22833322 |doi=10.1007/s11892-012-0308-1 }}</ref>{{MEDRS|date=December 2012}} ==Induced pluripotent== {{Main|Induced pluripotent stem cell}} These are not adult stem cells, but rather adult cells (e.g. epithelial cells) reprogrammed to give rise to 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.<ref name="Economist2007_11_22">{{cite news|title=Making human embryonic stem cells|publisher=The Economist|url=http://www.economist.com/science/displaystory.cfm?story_id=10170972|date=2007-11-22}}</ref><ref>{{cite web|url=http://www.npr.org/templates/story/story.php?storyId=16466265|publisher=[[National Public Radio]]|title=Skin Cells Can Become Embryonic Stem Cells|author=Brand, Madeleine; Palca, Joe and Cohen, Alex |date=2007-11-20}}</ref><ref>{{cite web|url=http://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}}</ref> [[Shinya Yamanaka]] and his colleagues at [[Kyoto University]] used the transcription factors Oct3/4, Sox2, c-Myc, and Klf4<ref name="Economist2007_11_22"/> in their experiments on cells from human faces. [[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,<ref name="Economist2007_11_22"/> 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 [[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=http://www.telegraph.co.uk/science/science-news/3314696/Dolly-creator-Prof-Ian-Wilmut-shuns-cloning.html|title=Dolly creator Prof Ian Wilmut shuns cloning|author=Highfield, Roger |date=2007-11-16|publisher=[[The Daily Telegraph|The Telegraph]] | location=London}}</ref> Frozen blood samples can be used as a source of induced pluripotent stem cells, opening a new avenue for obtaining the valued cells.<ref>[https://web.archive.org/web/20100703175036/http://www.newsdaily.com/stories/tre6604si-us-stemcells-frozen/ Frozen blood a source of stem cells, study finds]. newsdaily.com (2010-07-01)</ref> ==Lineage== {{Main|Stem cell line}} To ensure self-renewal, stem cells undergo two types of cell division (see ''Stem cell division and differentiation'' diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a [[progenitor cell]] with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally [[cell differentiation|differentiating]] into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as [[receptor (biochemistry)|receptors]]) between the daughter cells.<ref> {{cite journal |author=Beckmann J, Scheitza S, Wernet P, Fischer JC, Giebel B |title=Asymmetric cell division within the human hematopoietic stem and progenitor cell compartment: identification of asymmetrically segregating proteins |journal=Blood |volume=109 |issue=12 |pages=5494–501 |year=2007 |pmid=17332245 |doi=10.1182/blood-2006-11-055921 }}</ref> An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in ''Drosophila'' germarium have identified the signals [[decapentaplegic]] and adherens junctions that prevent germarium stem cells from differentiating.<ref> {{cite journal | author = Xie T, Spradling A | title = decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary | journal = Cell | volume = 94 | issue = 2 | pages = 251–60 | year = 1998 | pmid = 9695953 | doi = 10.1016/S0092-8674(00)81424-5 }}</ref><ref> {{cite journal | author = Song X, Zhu C, Doan C, Xie T | title = Germline stem cells anchored by adherens junctions in the Drosophila ovary niches | journal = Science | volume = 296 | issue = 5574 | pages = 1855–7 | year = 2002 | pmid = 12052957 | doi=10.1126/science.1069871 | bibcode = 2002Sci...296.1855S | last2 = Zhu | last3 = Doan | last4 = Xie }}</ref> The signals that lead to reprogramming of cells to an embryonic-like state are also being investigated. These signal pathways include several [[transcription factor]]s including the [[oncogene]] [[Myc|c-Myc]]. Initial studies indicate that transformation of mice cells with a combination of these anti-differentiation signals can reverse differentiation and may allow adult cells to become pluripotent.<ref name="Takahashi2006" /> However, the need to transform these cells with an oncogene may prevent the use of this approach in therapy. Challenging the terminal nature of cellular differentiation and the integrity of lineage commitment, it was recently determined that the somatic expression of combined [[transcription factor]]s can [[Induced stem cells#Induced progenitor stem cells|directly induce]] other defined somatic cell fates; researchers identified three neural-lineage-specific transcription factors that could directly convert mouse [[fibroblasts]] (skin cells) into fully functional [[neuron]]s. This "induced neurons" (iN) cell research inspires the researchers to induce other cell types. It implies that ''all'' cells are [[totipotent]]: with the proper tools, all cells may form all kinds of tissue.<ref>{{cite journal |title=Direct conversion of fibroblasts to functional neurons by defined factors |author=Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M |date=2010-02-25 |volume=463 |issue=7284 |pages=1035–41 |journal=Nature |pmid=20107439 |laysummary=http://www.dailymail.co.uk/health/article-1246591/Scientists-transform-skin-cells-brain-cells-pioneering-study-benefit-sufferers-Alzheimers-Parkinsons.html |doi=10.1038/nature08797 |pmc=2829121 |bibcode=2010Natur.463.1035V |last2=Ostermeier |last3=Pang |last4=Kokubu |last5=Südhof |last6=Wernig }}</ref> ==Treatments== {{Main|Stem cell treatments}} [[File:Stem cell treatments.svg|thumb|330px|Diseases and conditions where stem cell treatment is promising or emerging.<ref> Diabetes, rheumatoid arthritis, Parkinson's, Alzheimer's disease, osteoarthritis: *[http://stemcells.nih.gov/info/basics/pages/basics6.aspx Stem Cell Basics: What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized?]. In Stem Cell Information World Wide Web site. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2009. cited Sunday, April 26, 2009 Stroke and traumatic brain injury repair: *Steinberg, Douglas (November 2000) [http://www.mult-sclerosis.org/news/Dec2000/StemCellDebatePartII.html Stem Cells Tapped to Replenish Organs] thescientist.com Learning defects: *[http://www.israel21c.org/health/israeli-scientists-reverse-brain-birth-defects-using-stem-cells ISRAEL21c: Israeli scientists reverse brain birth defects using stem cells] December 25, 2008. (Researchers from the Hebrew University of Jerusalem-Hadassah Medical led by Prof. Joseph Yanai) Spinal cord injury repair: *{{cite journal |author=Kang KS |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=368–73 |year=2005 |pmid=16162459 |doi=10.1080/14653240500238160 |author2=Kim SW |author3=Oh YH |last4=Yu |first4=JW |last5=Kim |first5=K-Y |last6=Park |first6=HK |last7=Song |first7=C-H |last8=Han |first8=H}} Heart infarction: *{{cite journal |author=Strauer BE, Schannwell CM, Brehm M |title=Therapeutic potentials of stem cells in cardiac diseases |journal=Minerva Cardioangiol |volume=57 |issue=2 |pages=249–67 |year=2009 |pmid=19274033}} Anti-cancer: *[http://www.mult-sclerosis.org/news/Dec2000/StemCellDebatePartII.html Stem Cells Tapped to Replenish Organs] thescientist.com, Nov 2000. By Douglas Steinberg Baldness: *[https://web.archive.org/web/20080530042215rn_3/www.webmd.com/skin-problems-and-treatments/hair-loss/news/20041104/hair-cloning-nears-reality-as-baldness-cure ''Hair Cloning Nears Reality as Baldness Cure''] [[WebMD]] November 2004 Replace missing teeth: *{{cite journal |author=Yen AH, Sharpe PT |title=Stem cells and tooth tissue engineering |journal=Cell Tissue Res. |volume=331 |issue=1 |pages=359–72 |year=2008 |pmid=17938970 |doi=10.1007/s00441-007-0467-6}} Repair hearing: *[http://www.newscientist.com/article/dn7003 Gene therapy is first deafness 'cure' – health – 14 February 2005 – New Scientist] Restore vision: *[http://news.bbc.co.uk/1/hi/england/southern_counties/4495419.stm BBC NEWS | England | Southern Counties | Stem cells used to restore vision] Amyotrophic lateral sclerosis: *{{cite doi|10.1001/jama.285.13.1691}} Crohn's disease: *{{cite news | author=Anderson, Querida | title= Osiris Trumpets Its Adult Stem Cell Product | url=http://www.genengnews.com/articles/chitem.aspx?aid=2508 | work=[[Genetic Engineering & Biotechnology News]] | publisher=[[Mary Ann Liebert, Inc.]] | page=13 | date=2008-06-15 | accessdate=2008-07-06 | quote=(subtitle) Procymal is being developed in many indications, GvHD being the most advanced }} Wound healing: *{{cite journal | doi = 10.1146/annurev.med.58.082405.095329 | last1 = Gurtner | first1 = GC | last2 = Callaghan | first2 = MJ | last3 = Longaker | first3 = MT.| year = 2007 | title = Progress and potential for regenerative medicine | journal = Annu. Rev. Med | volume = 58 | issue = 1| pages = 299–312 | pmid = 17076602 }} </ref> Bone marrow transplantation is, as of 2009, the only established use of stem cells.]] Medical researchers believe that stem cell therapy has the potential to dramatically change the treatment of human disease. A number of adult stem cell therapies already exist, particularly [[bone marrow transplant]]s that are used to treat [[leukemia]].<ref> {{cite journal |author=Gahrton G, Björkstrand B |title=Progress in haematopoietic stem cell transplantation for multiple myeloma |journal=J Intern Med |volume=248 |issue=3 |pages=185–201 |year=2000 |pmid= 10971785 |doi=10.1046/j.1365-2796.2000.00706.x }}</ref> In the future, medical researchers anticipate being able to use technologies derived from stem cell research to treat a wider variety of diseases including [[cancer]], [[Parkinson's disease]], [[spinal cord injuries]], [[Amyotrophic lateral sclerosis]], [[multiple sclerosis]], and [[muscle]] damage, amongst a number of other impairments and conditions.<ref> {{cite journal |author=Lindvall O |title=Stem cells for cell therapy in Parkinson's disease |journal=Pharmacol Res |volume=47 |issue=4 |pages=279–87 |year=2003 |pmid = 12644384 |doi=10.1016/S1043-6618(03)00037-9 }}</ref><ref> {{cite journal |author=Goldman S, Windrem M |title=Cell replacement therapy in neurological disease |journal=Philos Trans R Soc Lond B Biol Sci |volume=361 |issue=1473 |pages=1463–75 |year=2006 |pmid = 16939969 |doi=10.1098/rstb.2006.1886 |pmc=1664668 }}</ref> However, there still exists a great deal of social and scientific uncertainty surrounding stem cell research, which could possibly be overcome through public debate and future research, and further education of the public. One concern of treatment is the risk that transplanted stem cells could form tumors and become cancerous if cell division continues uncontrollably.<ref> "Stem-cell therapy: Promise and reality." Consumer Reports on Health 17.6 (2005): 8–9. Academic Search Premier. EBSCO. Web. 5 Apr. 2010.</ref> Stem cells are widely studied, for their potential therapeutic use and for their inherent interest.<ref> {{cite news |author=Wade N |title=Some Scientists See Shift in Stem Cell Hopes |publisher=New York Times |url=http://www.nytimes.com/2006/08/14/washington/14stem.html?_r=1 |date=2006-08-14 |accessdate=2006-12-28 }}</ref> Supporters of embryonic stem cell research argue that such research should be pursued because the resultant treatments could have significant medical potential. It has been proposed that surplus embryos created for [[in vitro fertilization]] could be donated with consent and used for the research. The recent development of [[iPS cells]] has been called a bypass of the legal controversy. Laws limiting the destruction of human embryos have been credited for being the reason for development of iPS cells, but it is still not completely clear whether hiPS cells are equivalent to hES cells. Recent work demonstrates hotspots of aberrant epigenomic reprogramming in hiPS cells (Lister, R., et al., 2011). ===Disadvantages=== Stem cell treatments may require immunosuppression because of a requirement for radiation before the transplant to remove the patient'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 cells from the same patient that 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>Moore, Keith L., T.V.N. Persaud, and Mark G. Torchia. Before We Are Born: Essentials of Embryology and Birth Defects. Philadelphia, PA: Saunders, Elsevier. 2013 Print.</ref> Some stem cells form tumors after transplantation; pluripotency is linked to tumor formation especially in embryonic stem cells, fetal proper stem cells, induced pluripotent stem cells. Fetal proper stem cells form tumors despite multipotency.{{Citation needed|date=November 2013}} [[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 |author= Greenhough S, Hay DC. |title=Stem Cell-Based Toxicity Screening: Recent Advances in Hepatocyte Generation |url=http://adisonline.com/pharmaceuticalmedicine/Abstract/2012/26020/Stem_Cell_Based_Toxicity_Screening__Recent.2.aspx |journal=Pharm Med |volume=26 |issue=2 |pages=85–89 |year=2012 |doi= 10.1007/BF03256896}}</ref> ==Research patents== The [[patent]]s covering a lot of work on human embryonic stem cells are owned by the [[Wisconsin Alumni Research Foundation]] (WARF). WARF does not charge academics to study human stem cells but does charge commercial users. WARF sold [[Geron Corp.]] exclusive rights to work on human stem cells but later sued Geron Corp. to recover some of the previously sold rights. The two sides agreed that Geron Corp. would keep the rights to only three cell types. In 2001, WARF came under public pressure to widen access to human stem-cell technology.<ref name = "stemcellPatent">Regalado, Antonio, David P. Hamilton (July 2006). [http://www.geneticsandsociety.org/article.php?id=1896 "How a University's Patents May Limit Stem-Cell Researcher."] ''The Wall Street Journal''. Retrieved on July 24, 2006.</ref> A request for reviewing the WARF patents 5,843,780; 6,200,806; 7,029,913 [[US Patent and Trademark Office]] were filed by non-profit patent-watchdogs [http://www.consumerwatchdog.org/ The Foundation for Taxpayer & Consumer Rights], and the [[Public Patent Foundation]] as well as molecular biologist Jeanne Loring of the Burnham Institute. According to them, two of the patents granted to WARF are invalid because they cover a technique published in 1993 for which a patent had already been granted to an Australian researcher. Another part of the challenge states that these techniques, developed by [[James Thomson (cell biologist)|James A. Thomson]], are rendered obvious by a 1990 paper and two textbooks. Based on this challenge, patent 7,029,913 was rejected in 2010. The two remaining hES WARF patents are due to expire in 2015. ==Key research events== {{Very long|section|date=December 2013}} *1908: The term "stem cell" was proposed for scientific use by the [[Russia]]n histologist [[Alexander Maksimov]] (1874–1928) at congress of hematologic society in [[Berlin]]. It postulated existence of haematopoietic stem cells. *1960s: [[Joseph Altman]] and Gopal Das present scientific evidence of adult [[neurogenesis]], ongoing stem cell activity in the brain; their reports contradict [[Santiago Ramón y Cajal|Cajal]]'s "no new neurons" dogma and are largely ignored. *1963: [[Ernest McCulloch|McCulloch]] and [[James Till|Till]] illustrate the presence of self-renewing cells in mouse bone marrow. *1968: [[Bone marrow]] [[Organ transplant|transplant]] between two siblings successfully treats [[Severe combined immunodeficiency|SCID]]. *1978: [[Haematopoietic stem cell]]s are discovered in human [[cord blood]]. *1981: Mouse [[embryonic stem cell]]s are derived from the [[inner cell mass]] by scientists [[Martin Evans]], [[Matthew Kaufman]], and [[Gail R. Martin]]. Gail Martin is attributed for coining the term "Embryonic Stem Cell".<ref>{{cite web |url= http://www.ucsf.edu/about/stem-cells/overview |title= Stem Cells - Overview| publisher= University of California San Francisco |accessdate=19 December 2013}}</ref> *1992: [[Neural stem cell]]s are cultured ''[[in vitro]]'' as neurospheres. *1995: [[B.G. Matapurkar|Dr. B.G. Matapurkar]] pioneers in adult stem-cell research with clinical utilization of research in the body and neo-regeneration of tissues and organs in the body. Received International Patent from US Patent Office (USA) in 2001 (effective from 1995). Clinical utilization in human body also demonstrated and patented in 60 patients (World Journal of Surgery-1999<ref>{{cite pmid|10085391}}</ref> and 1991<ref>{{cite pmid|1767543}}</ref>). *1997: Dr. B.G. Matapurkar's surgical technique on regeneration of tissues and organs is published.<ref>{{cite book|last=Maingot|first=Rodney|title=Abdominal Operations|year=1997|isbn=0838561063}}</ref> Regeneration of fallopian tube and uterus is published.<ref>{{cite book|title=Textbook of Gynaecology|year=2010|publisher=JP Publications|isbn=9350253690|pages=620–625}}</ref> *1997: Leukemia is shown to originate from a haematopoietic stem cell, the first direct evidence for [[cancer stem cell]]s. *1998: [[James Thomson (cell biologist)|James Thomson]] and coworkers derive the first human embryonic [[stem cell line]] at the [[University of Wisconsin–Madison]].<ref name=pmid9804556> {{cite journal | author = 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 | location=New York | volume = 282 | issue = 5391 | pages = 1145–7 | year = 1998 | pmid = 9804556 | doi = 10.1126/science.282.5391.1145 | bibcode = 1998Sci...282.1145T | last2 = Itskovitz-Eldor | last3 = Shapiro | last4 = Waknitz | last5 = Swiergiel | last6 = Marshall | last7 = Jones }}</ref> *1998: John Gearhart (Johns Hopkins University) extracted germ cells from fetal gonadal tissue (primordial germ cells) before developing pluripotent stem cell lines from the original extract. *2000s: Several reports of [[adult stem cell]] plasticity are published. *2001: Scientists at [[Advanced Cell Technology]] clone first early (four- to six-cell stage) human embryos for the purpose of generating embryonic stem cells.<ref> {{cite journal |author=Cibelli JB, Lanza RP, West MD, Ezzell C |title=The first human cloned embryo |journal=Scientific American |volume=286 |pages=44 |date=November 2001 |url=http://www.scientificamerican.com/article.cfm?id=the-first-human-cloned-em |bibcode=2002SciAm.286a..44C |last2=Lanza |last3=West |last4=Ezzell |doi=10.1038/scientificamerican0102-44 }}</ref> *2003: Dr. Songtao Shi of NIH discovers new source of adult stem cells in children's primary teeth.<ref>{{cite journal | author=Shostak S | title=(Re)defining stem cells | journal=BioEssays | year=2006 | pages=301–8 | volume=28 | issue=3 | pmid = 16479584 | doi=10.1002/bies.20376 }}</ref> *2004–2005: Korean researcher [[Hwang Woo-Suk]] claims to have created several human [[embryonic stem cell]] lines from unfertilised human [[oocyte]]s. The lines were later shown to be fabricated. *2005: Researchers at [[Kingston University]] in [[England]] claim to have discovered a third category of stem cell, dubbed cord-blood-derived embryonic-like stem cells (CBEs), derived from umbilical [[cord blood]]. The group claims these cells are able to differentiate into more types of tissue than adult stem cells. *2005: Researchers at [[UC Irvine]]'s Reeve-Irvine Research Center are able to partially restore the ability of rats with paralyzed spines to walk through the injection of human [[neural stem cell]]s.<ref>{{cite journal|last=Keirstead|first=HS|coauthors=Nistor G, Bernal G, Totoiu M, Cloutier F, Sharp K, Steward O.|title=Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury|journal=The Journal of Neuroscience|year=2005|volume=25|issue=19|pages=4694–4705|doi=10.1523/JNEUROSCI.0311-05.2005|pmid=15888645}}</ref> [[File:Yong Zhao smiling Portrait.png|thumb|Yong Zhao, University of Illinois at Chicago]] *April 2006 Scientists at the University of Illinois at Chicago identified [[Cord Blood-Derived Multipotent Stem Cells (CB-SCs)|novel stem cells]] from the [[cord blood|umbilical cord blood]] with [[Embryonic stem cells|embryonic]] and [[hematopoietic]] characteristics.<ref name="Identification" /> *August 2006: Mouse [[Induced pluripotent stem cell]]s: the journal ''[[Cell (journal)|Cell]]'' publishes Kazutoshi Takahashi and [[Shinya Yamanaka]].<ref name="Takahashi2006" /> *November 2006: Yong Zhao et al. revealed the [[Immunomics|immune regulation]] of [[T lymphocyte]]s by [[Cord Blood-Derived Multipotent Stem Cells (CB-SCs)]].<ref name="Immune" /> *October 2006: Scientists at [[Newcastle University]] in England create the first ever artificial liver cells using umbilical cord blood stem cells.<ref> {{cite web |url=http://discovermagazine.com/2007/mar/good-news-for-alcoholics |title=Good news for alcoholics |publisher=Discover Magazine |date=March 2007 |accessdate=2010-02-28 }}</ref><ref> {{cite news |url=http://news.scotsman.com/health.cfm?id=1608072006 |archiveurl=http://web.archive.org/web/20070203010452/http://news.scotsman.com/health.cfm?id=1608072006 |archivedate=2007-02-03 |publisher=The Scotsman |location=Edinburgh |first=Shã‚N |last=Ross |title=First liver grown from stem cells offers hope for transplant patients |date=2006-10-31 }}</ref> *January 2007: Scientists at [[Wake Forest University]] led by Dr. [[Anthony Atala]] and [[Harvard University]] report discovery of a new type of stem cell in [[amniotic fluid]].<ref> {{cite journal |title=Isolation of amniotic stem cell lines with potential for therapy |journal=Nat Biotechnol |volume=25 |issue=1 |pages=100–6 |year=2007 |pmid=17206138 |doi=10.1038/nbt1274 |last4=Xu |first4=Tao |last5=Santos |first5=Cesar C |last6=Perin |first6=Laura |last7=Mostoslavsky |first7=Gustavo |last8=Serre |first8=Angéline C |last9=Snyder |first9=Evan Y |last10=Yoo |first10=James J |last11=Furth |first11=Mark E |last12=Soker |first12=Shay |last13=Atala |first13=Anthony |display-authors=8 |last1 = Coppi|first1 = P.D.}}</ref> This may potentially provide an alternative to embryonic stem cells for use in research and therapy.<ref>{{cite news |url=http://www.boston.com/news/nation/articles/2007/01/08/easy_stem_cell_source_sparks_interest/ |title=Easy stem-cell source sparks interest: Researchers find amniotic fluid offers advantages |publisher=Boston Globe |author=Kaplan, Karen |date=8 January 2007 }}</ref> *June 2007: Research reported by three different groups shows that normal skin cells can be reprogrammed to an embryonic state in mice.<ref> {{cite journal | author=Cyranoski D | title=Simple switch turns cells embryonic | journal=Nature | year=2007 | pages=618–9 | volume=447 | issue=7145 | pmid = 17554270 | doi = 10.1038/447618a | bibcode=2007Natur.447..618C }}</ref> In the same month, scientist [[Shoukhrat Mitalipov]] reports the first successful creation of a primate stem cell line through [[somatic cell nuclear transfer]]<ref> {{cite journal | author=Mitalipov SM, Zhou Q, Byrne JA, Ji WZ, Norgren RB, Wolf DP | title=Reprogramming following somatic cell nuclear transfer in primates is dependent upon nuclear remodeling | journal=Hum Reprod | year=2007 | pages=2232–42 | volume=22 | issue=8 | pmid = 17562675 | doi = 10.1093/humrep/dem136 }}</ref> [[File:Martin Evans Nobel Prize.jpg|thumb|upright|Martin Evans, a co-winner of the Nobel Prize in recognition of his gene targeting work.]] *October 2007: [[Mario Capecchi]], [[Martin Evans]], and [[Oliver Smithies]] win the 2007 [[Nobel Prize for Physiology or Medicine]] for their work on embryonic stem cells from mice using gene targeting strategies producing genetically engineered mice (known as [[knockout mice]]) for gene research.<ref name = "Nobel 2007">{{cite web |url = http://nobelprize.org/nobel_prizes/medicine/laureates/2007/index.html |title = The Nobel prize in physiology or medicine 2007 |accessdate = 8 October 2007 |publisher = Nobelprize.org}}</ref> *November 2007: Human induced pluripotent stem cells: Two similar papers released by their respective journals prior to formal publication: in ''[[Cell (journal)|Cell]]'' by [[Kazutoshi Takahashi]] and [[Shinya Yamanaka]], "Induction of pluripotent stem cells from adult human fibroblasts by defined factors",<ref>{{cite journal |author=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=861–72 |year=2007 |pmid=18035408 |doi=10.1016/j.cell.2007.11.019 |url=http://images.cell.com/images/Edimages/Cell/IEPs/3661.pdf |format=PDF }}</ref> and in ''Science'' by [[Junying Yu]], et al., from the research group of [[James Thomson (cell biologist)|James Thomson]], "Induced pluripotent stem cell lines derived from human somatic cells":<ref> {{cite journal |author=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 (journal)|Science]] |volume=318 |issue=5858 |pages=1917–20 |year=2007 |pmid=18029452 |doi=10.1126/science.1151526 |bibcode=2007Sci...318.1917Y |last2=Vodyanik |last3=Smuga-Otto |last4=Antosiewicz-Bourget |last5=Frane |last6=Tian |last7=Nie |last8=Jonsdottir |last9=Ruotti |last10=Stewart |last11=Slukvin |last12=Thomson }}</ref> pluripotent stem cells generated from mature human fibroblasts. It is possible now to produce a stem cell from almost any other human cell instead of using embryos as needed previously, albeit the risk of [[tumorigenesis]] due to [[c-myc]] and [[Gene therapy#Retroviruses|retroviral gene transfer]] remains to be determined. *January 2008: Robert Lanza and colleagues at Advanced Cell Technology and UCSF create the first human embryonic stem cells without destruction of the embryo<ref> {{cite doi|10.1016/j.stem.2007.12.013}}</ref> *January 2008: Development of human cloned blastocysts following [[somatic cell nuclear transfer]] with adult fibroblasts<ref> {{cite journal |url=http://stemcells.alphamedpress.org/cgi/reprint/2007-0252v1.pdf |archiveurl=http://web.archive.org/web/20080625032536/http://stemcells.alphamedpress.org/cgi/reprint/2007-0252v1.pdf |archivedate=2008-06-25 |title=Development of human cloned blastocysts following somatic cell nuclear transfer (SCNT) with adult fibroblasts |author=French AJ, Adams CA, Anderson LS, Kitchen JR, Hughes MR, Wood SH |journal=Stem Cells Express |year=2008 |doi=10.1634/stemcells.2007-0252 |volume=26 |pmid=18202077 |issue=2 |pages=485–93 }}</ref> *February 2008: Generation of pluripotent stem cells from adult mouse liver and stomach: these iPS cells seem to be more similar to embryonic stem cells than the previously developed iPS cells and not tumorigenic, moreover genes that are required for iPS cells do not need to be inserted into specific sites, which encourages the development of non-viral reprogramming techniques.<ref> {{cite journal |author=Aoi T |title=Generation of pluripotent stem cells from adult mouse liver and stomach cells |journal=Science |volume=321 |issue=5889 |pages=699–702 |year=2008 |pmid=18276851 |doi=10.1126/science.1154884 |author2=Yae K |author3=Nakagawa M |last4=Ichisaka |first4=T. |last5=Okita |first5=K. |last6=Takahashi |first6=K. |last7=Chiba |first7=T. |last8=Yamanaka |first8=S. |bibcode=2008Sci...321..699A }}</ref> *March 2008-The first published study of successful cartilage regeneration in the human knee using autologous adult mesenchymal stem cells is published by clinicians from Regenerative Sciences<ref> {{cite journal |author=Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D |title=Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells |journal=Pain Physician |volume=11 |issue=3 |pages=343–53 |year=2008 |pmid=18523506 |url=http://www.painphysicianjournal.com/linkout_vw.php?issn=1533-3159&vol=11&page=343 |issn=1533-3159 }}</ref> *October 2008: Sabine Conrad and colleagues at Tübingen, Germany generate [[pluripotent stem cells]] from spermatogonial cells of adult human testis by culturing the cells in vitro under [[leukemia inhibitory factor]] (LIF) supplementation.<ref> {{cite journal |author=Conrad S |title=Generation of pluripotent stem cells from adult human testis |journal=Nature |volume=456 |issue=7220 |pages=344–9 |year=2008 |pmid=18849962 |doi=10.1038/nature07404 |author2=Renninger M |author3=Hennenlotter J |last4=Wiesner |first4=Tina |last5=Just |first5=Lothar |last6=Bonin |first6=Michael |last7=Aicher |first7=Wilhelm |last8=Bühring |first8=Hans-Jörg |last9=Mattheus |first9=Ulrich |last10=Mack |first10=Andreas |last11=Wagner |first11=Hans-Joachim |last12=Minger |first12=Stephen |last13=Matzkies |first13=Matthias |last14=Reppel |first14=Michael |last15=Hescheler |first15=Jürgen |last16=Sievert |first16=Karl-Dietrich |last17=Stenzl |first17=Arnulf |last18=Skutella |first18=Thomas |display-authors=8 |bibcode=2008Natur.456..344C }}</ref> *30 October 2008: Embryonic-like stem cells from a single human hair.<ref> {{cite journal |author=Baker M |title=Embryonic-like stem cells from a single human hair |journal=Nature Reports Stem Cells |year=2008 |doi=10.1038/stemcells.2008.142 }}</ref> *January 2009: Yong Zhao and colleagues confirmed the reversal of autoimmune-caused type 1 diabetes by [[Cord Blood-Derived Multipotent Stem Cells (CB-SCs)]] in an animal experiment.<ref name="Human modulated" /><ref name="New type" /> *1 March 2009: Andras Nagy, Keisuke Kaji, ''et al.'' discover a way to produce embryonic-like stem cells from normal adult cells by using a novel "wrapping" procedure to deliver specific genes to adult cells to reprogram them into stem cells without the risks of using a virus to make the change.<ref> {{cite journal |journal=Nature |title=piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells |author=Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hämäläinen R, Cowling R, Wang W, Liu P, Gertsenstein M, Kaji K, Sung HK, Nagy A |doi=10.1038/nature07863 |date=2009-03-01 |volume=458 |pmid=19252478 |issue=7239 |pages=766–70 |bibcode=2009Natur.458..766W |last2=Michael |last3=Mohseni |last4=Desai |last5=Mileikovsky |last6=Hämäläinen |last7=Cowling |last8=Wang |last9=Liu |last10=Gertsenstein |last11=Kaji |last12=Sung |last13=Nagy }}</ref><ref> {{cite web |url=http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20090227/stem_cells_090228/20090301?hub=TopStories |title=Canadians make stem cell breakthrough |accessdate=March 1, 2009 |date=March 1, 2009 }}</ref><ref> {{cite news |agency=Canadian Press |publisher=Amherst Daily News |url=http://www.amherstdaily.com/index.cfm?sid=227086&sc=510 |title=Researchers find new method for turning adult cells into stem cells |date=2009-01-03 |accessdate=2010-02-28 }}</ref> The use of [[electroporation]] is said to allow for the temporary insertion of genes into the cell.<ref name=Sample> {{cite news |author=Sample, Ian |url=http://www.guardian.co.uk/science/2009/mar/01/stem-cells-breakthrough |title=Scientists' stem cell breakthrough ends ethical dilemma |publisher=The Guardian |date=2009-03-01 |accessdate=2009-03-03 | location=London }}</ref><ref name=Sample/><ref> {{cite journal |journal=Nature |year=2009 |title=Virus-free induction of pluripotency and subsequent excision of reprogramming factors |author=Kaji K, Norrby K, Paca A, Mileikovsky M, Mohseni P, Woltjen K |doi=10.1038/nature07864 |volume=458 |pmid=19252477 |issue=7239 |pmc=2667910 |pages=771–5 |bibcode=2009Natur.458..771K |last2=Norrby |last3=Paca |last4=Mileikovsky |last5=Mohseni |last6=Woltjen }}</ref><ref>{{cite journal|journal=Stem Cells |year=2009 |volume=27 |issue=5 |pages=1098–1108 |title=Methylguanine DNA methyltransferase-mediated drug resistance-based selective enrichment and engraftment of transplanted stem cells in skeletal muscle |author=Lee ASJ, Kahatapitiya P, Kramer B, Joya JE, Hook J, Liu R, Schevzov G, Alexander IE, McCowage G, Montarras D, Gunning PW, Hardeman EC|doi=10.1002/stem.28|pmid=19415780}}</ref> *28 May 2009 Kim ''et al.'' announced that they had devised a way to manipulate skin cells to create patient specific "induced pluripotent stem cells" (iPS), claiming it to be the 'ultimate stem cell solution'.<ref> {{cite journal |title=Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins |author=Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS |pmid=19481515 |journal=Cell Stem Cell |laysummary= http://www.reuters.com/article/idUSN28256624 |date=27 May 2009 |volume=4 |issue=6 |pages=472–6 |doi=10.1016/j.stem.2009.05.005 |pmc=2705327 }} (cited in lay summary, not read)</ref> *11 October 2010 First trial of embryonic stem cells in humans.<ref>{{cite news| url=http://www.bbc.co.uk/news/health-11517680 | work=BBC News | title=First trial of embryonic stem cells in humans | date=2010-10-11}}</ref> *25 October 2010: Ishikawa ''et al.'' write in the Journal of Experimental Medicine that research shows that transplanted cells that contain their new host's nuclear DNA could still be rejected by the invidual's immune system due to foreign [[mitochondrial DNA]]. Tissues made from a person's stem cells could therefore be rejected, because mitochondrial genomes tend to accumulate mutations.<ref> {{cite journal |title=The innate immune system in host mice targets cells with allogenic mitochondrial DNA |author=Ishikawa K, Toyama-Sorimachi N, Nakada K, Morimoto M, Imanishi H, Yoshizaki M, Sasawatari S, Niikura M, Takenaga K, Yonekawa H, Hayashi J |pmid=20937705 |journal=J Exp Med. |year=2010 |volume=207 |issue=11 |pages=2297–305 |doi=10.1084/jem.20092296 |pmc=2964578 }}</ref> *2011: [[Israel]]i scientist Inbar Friedrich Ben-Nun led a team which produced the first stem cells from endangered species, a breakthrough that could save animals in danger of extinction.<ref>Shtull-Trauring, Asaf (2011-09-06) [http://www.haaretz.com/print-edition/news/israeli-scientist-leads-breakthrough-stem-cell-research-on-endangered-species-1.382754 Israeli scientist leads breakthrough stem cell research on endangered species ] </ref> *January 2012: The human clinical trial of treating [[type 1 diabetes]] with [[Stem Cell Educator Therapy|lymphocyte modification]] using [[Cord Blood-Derived Multipotent Stem Cells (CB-SCs)]] achieved an improvement of C-peptide levels, reduced the median glycated hemoglobin A1C (HbA1c) values, and decreased the median daily dose of insulin in both human patient groups with and without residual beta cell function.<ref name="Reversal" /><ref name="immune balance" /> Yong Zhao's [[Stem Cell Educator Therapy]] appears "so simple and so safe"<ref> {{cite news | url=http://usatoday30.usatoday.com/news/health/story/health/story/2012-01-14/Novel-stem-cell-treatment-may-hold-promise-for-type-1-diabetes/52536006/1 | title=USA Today | work=Novel stem cell treatment may hold promise for type 1 diabetes | date=January 13, 2012 | accessdate=December 11, 2012 | author=Gordon, Serena}} </ref> *October 2012: Positions of nucleosomes in mouse embryonic stem cells and the changes in their positions during differentiation to neural progenitor cells and embryonic fibroblasts are determined with single-nucleotide resolution.<ref name="pmid23085715">{{cite journal |author=Teif VB, Vainshtein Y, Caudron-Herger M, Mallm JP, Marth C, Höfer T, Rippe K. |title=Genome-wide nucleosome positioning during embryonic stem cell development. |journal=Nat Struct Mol Biol. |year=2012 |doi=10.1038/nsmb.2419 |volume=19 |issue=11 |pages=1185–92 |pmid=23085715 }}</ref> *2012: Katsuhiko Hayashi used mouse skin cells to create stem cells and then used these stem cells to create mouse eggs. These eggs were then fertilized and produced healthy baby offspring. These latter mice were able to have their own babies.<ref>{{cite journal|doi=10.1126/science.1226889}}</ref> * 2013: First time lab grown meat made from muscle stem-cells has been cooked and tasted.<ref>{{cite web|author=Alok Jha, science correspondent |url=http://www.theguardian.com/science/2013/aug/05/lab-grown-hamburger-synthetic-meat |title=Anyone for a stem-cell burger? |publisher=The Guardian |date=5 August 2013 |accessdate=2014-02-04}}</ref> *2013: First time mice adult cells were reprogrammed into stem cells in vivo.<ref>{{cite web|author=jobs |url=http://www.nature.com/news/stem-cells-created-in-living-mice-1.13725 |title=Stem cells created in living mice |work=Nature News & Comment |publisher=Nature.com |date=11 September 2013 |accessdate=2014-02-04}}</ref> * 2013: Scientists at Scotland's [[Heriot-Watt University]] developed a 3D printer that can produce clusters of living human [[embryonic stem cell]]s, potentially allowing [[organ transplant|complete organs]] to be printed on demand in the future.<ref>{{cite web|url=http://www.bbc.co.uk/news/uk-scotland-edinburgh-east-fife-21328109|title=Edinburgh scientists use 3D printing to produce stem cells|publisher=BBC|date=5 February 2013|accessdate=5 February 2013}}</ref> * 2014: Adult mouse cells reprogrammed to pluripotent stem cells using [[Stimulus-triggered_acquisition_of_pluripotency_cell|stimulus-triggered acquisition of pluripotency (STAP)]];<ref name=Grens2014>{{cite web | last = Kerry | first = Grens | title = New Method for Reprogramming Cells | publisher = scientist.com | date = 29 January 2014 | url = http://www.the-scientist.com/?articles.view/articleNo/39025/title/New-Method-for-Reprogramming-Cells/| accessdate = 2014-02-06 | archiveurl = | archivedate = }}</ref> a process which involved bathing blood cells in an acid bath (pH 5.7) for 30minutes at 37°C.<ref name=Aaacccid2014>{{cite web |editor=NHS Choices |author=Bazian |authorlink = http://www.bazian.com |title=Breakthrough in stem cell creation using acid bath |quote=They put them in a weak acid solution (pH 5.7) for 30 minutes at 37°C, and then put them into petri dishes and grew them at normal pH. |publisher=U.K. National Health Service |date=30 January 2014 |url=http://www.nhs.uk/news/2014/01January/Pages/Breakthrough-in-stem-cell-creation-using-acid-bath.aspx| accessdate = 2014-02-06 | archiveurl = | archivedate = }}</ref> ==See also== *[[Cell bank]] *[[Human genome]] *[[Meristem]] *[[Partial cloning]] *[[Plant stem cell]] *[[Stem cell controversy]] *[[Stem cell marker]] ==References== {{Reflist|30em}} ==External links== {{Commons category|Stem cells}} <!-- Please use the talk page to propose any additions to this section. If you do not do this, the link will almost certainly be deleted.--> ;General *[http://stemcells.nih.gov/info/basics/ Stem Cell Basics] Courtesy of the National Institutes of Health *[http://www.nature.com/stemcells Nature Reports Stem Cells: Introductory material, research advances and debates concerning stem cell research.] *[http://dels.nas.edu/bls/stemcells/booklet.shtml Understanding Stem Cells: A View of the Science and Issues from the National Academies] *[http://www.scientificamerican.com/article.cfm?id=the-stem-cell-challenge Scientific American Magazine (June 2004 Issue) The Stem Cell Challenge] *[http://www.scientificamerican.com/article.cfm?id=stem-cells-the-real-culpr-2006-07 Scientific American Magazine (July 2006 Issue) Stem Cells: The Real Culprits in Cancer?] *{{sep entry|stem-cells|Ethics of Stem Cell Research|Andrew Siegel}} *[http://www.nature.com/nbt/journal/v25/n1/abs/nbt1274.html Isolation of amniotic stem cell lines with potential for therapy] *[http://stemcell.childrenshospital.org/ Boston Children's Hospital Stem Cell Research] *[http://stemcelllist.com/ Stem Cell Research and Industry Directory] *[http://www.cesbank.org/ Corneal endothelial and epithelial stem cell research and application] *[http://www.stemcelltelevision.com/ Stem Cell Consumer Progress and Research] *[http://www.hopkinsmedicine.org/stem_cell_research Stem Cell Research at Johns Hopkins] * [http://www.slideshare.net/StemCellExperts/newstemcellslideshare?from_search=1 What Are Stem Cells?] * [http://www.foxnews.com/health/2012/07/03/7-things-should-know-about-cord-blood-banking/ 7 Things You Should Know About Cord Blood Banking] *[http://parentsguidecordblood.org/ Parent's Guide to Cord Blood Foundation], a non-profit cord blood educational foundation ;Peer-reviewed journals *[http://www.tandf.co.uk/journals/titles/14653249.asp Cytotherapy] *[http://www.liebertpub.com/products/product.aspx?pid=9 Cloning and Stem Cells] *[http://www.pubstemcell.com/ Journal of Stem Cells and Regenerative Medicine] *[http://www.liebertpub.com/products/product.aspx?pid=125 Stem Cells and Development] *[http://www.futuremedicine.com/loi/rme Regenerative Medicine] *[http://www.elsevier.com/wps/find/journaldescription.cws_home/711630/description#description Stem Cell Research] *[http://www.stembook.org/ StemBook] {{Wound healing}} {{Stem cells}} {{Breakthrough of the Year}} {{DEFAULTSORT:Stem Cell}} [[Category:Stem cells| ]] [[Category:Induced stem cells]] [[Category:Biotechnology]] [[Category:Cell biology]] [[Category:Cloning]] [[Category:Developmental biology]] This information was provided by genius Will Johnson.'