Stem cell
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2008-07-17T02:36:31Z
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[[WP:UNDO|Undid]] revision 226159884 by [[Special:Contributions/151.196.37.226|151.196.37.226]] ([[User talk:151.196.37.226|talk]])
[[Image:Mouse embryonic stem cells.jpg|right|thumb|300px|[[Mus musculus|Mouse]] [[Mammalian embryogenesis|embryo]]nic stem cells with fluorescent marker.]]
[[Image:Human embryonic stem cell colony phase.jpg|right|thumb|300px|Human Embryonic Stem cell colony on mouse embryonic fibroblast feeder layer.]]
'''Stem cells''' are [[Cell (biology)|cells]] found in most, if not all, multi-cellular [[organisms]]. They are characterized by the ability to renew themselves through [[Mitosis|mitotic]] [[cell division]] and [[Cellular differentiation|differentiating]] into a diverse range of specialized cell types. Research in the stem cell field grew out of findings by [[Canada|Canadian]] scientists [[Ernest McCulloch|Ernest A. McCulloch]] and [[James Till|James E. Till]] in the 1960s.<ref>{{cite journal | author = 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 | pages = 452–4 | year = 1963 | pmid = 13970094 | doi=10.1038/197452a0 }}</ref><ref>{{cite journal | author = 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| pages = 327–36 | year = 1963 | pmid = 14086156 | doi = 10.1002/jcp.1030620313 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
The two broad types of mammalian stem cells are: '''[[embryonic stem cell]]s''' that are found in [[blastocyst]]s, and '''[[adult stem cell]]s''' that are found in adult tissues. In a developing [[embryo]], stem cells can differentiate into all of the specialized embryonic tissues. In [[adult]] organisms, stem cells and [[progenitor cell]]s act as a repair system for the body, replenishing specialized cells, but also maintain the normal turnover of regenerative organs, such as blood, skin or intestinal tissues.
As stem cells can be grown and transformed into specialized cells with characteristics consistent with cells of various tissues such as muscles or nerves through [[cell culture]], their use in [[Cell therapy|medical therapies]] has been proposed. In particular, embryonic [[cell line]]s, [[autologous]] embryonic stem cells generated through [[therapeutic cloning]], and highly plastic adult stem cells from the [[umbilical cord blood]] or [[bone marrow]] are touted as promising candidates.<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>
==Properties of stem cells==
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 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.
===Potency definitions===
[[Image:Stem cells diagram.png|400px|thumb|right|Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.]]
''Potency'' specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.
* '''[[Totipotency|Totipotent]]''' stem 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. These cells can differentiate into embryonic and extraembryonic cell types.
* '''[[Pluripotent]]''' stem cells are the descendants of totipotent cells and can differentiate into cells derived from any of the three [[germ layer]]s.
* '''[[Multipotent]]''' stem cells can produce only cells of a closely related family of cells (e.g. [[hematopoietic stem cell]]s differentiate into red blood cells, white blood cells, platelets, etc.).
* '''[[Unipotency|Unipotent]]''' cells can produce only one cell type, but have the property of self-renewal which distinguishes them from non-stem cells (e.g. muscle stem cells).
===Identifying stem cells===
The practical definition of a stem cell is the functional definition - the ability to regenerate tissue over a lifetime. For example, the gold standard test for a bone marrow or hematopoietic stem cell (HSC) is the ability to transplant one cell and save an individual without HSCs. In this case, a stem cell must be able to produce new blood cells and immune cells over a long term, demonstrating potency. 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 [[mesenchymal stem cell|clonogenic assay]]s, where single cells are characterized by 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 = Exp Hematol | 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 = Exp Hematol | volume = 4 | issue = 5 | pages = 267–74 | year = 1976 | pmid = 976387 }}</ref> As well, stem cells can be isolated based on 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]]''. Considerable debate exists whether some proposed adult cell populations are truly stem cells.
==Embryonic stem cells==
{{main|Embryonic stem cell}}
'''Embryonic stem cell lines''' (ES cell lines) are cultures of cells derived from the [[epiblast]] tissue of the [[inner cell mass]] (ICM) of a [[blastocyst]] or earlier [[morula]] stage embryos.<ref>[http://www.foxnews.com/story/0,2933,210078,00.html FOXNews.com - New Stem-Cell Procedure Doesn't Harm Embryos, Company Claims - Biology | Astronomy | Chemistry | Physics<!-- Bot generated title -->]</ref> A blastocyst is an early stage [[embryo]]—approximately four to five days old in humans and consisting 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 taken place using 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 and require the presence of Leukemia Inhibitory Factor (LIF).<ref>[https://catalog.invitrogen.com/index.cfm?fuseaction=iProtocol.unitSectionTree&treeNodeID=9E662600C6C10276D8E040E99EA33BB0] , Mouse Embryonic Stem (ES) Cell Culture-Current Protocols in Molecular Biology </ref> 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>[http://stemcells.nih.gov/research/NIHresearch/scunit/culture.asp], Culture of Human Embryonic Stem Cells (hESC) NIH</ref> Without optimal culture conditions or genetic manipulation,<ref>{{cite journal |author=Chambers I, Colby D, Robertson M, ''et al'' |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}}</ref> embryonic stem cells will rapidly differentiate.
A human embryonic stem cell is also defined by the presence 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, Lee TI, Cole MF, ''et al'' |title=Core transcriptional regulatory circuitry in human embryonic stem cells |journal=Cell |volume=122 |issue=6 |pages=947–56 |year=2005 |pmid=16153702 |doi=10.1016/j.cell.2005.08.020}}</ref> The cell surface antigens most commonly used to identify hES cells are the glycolipids SSEA3 and SSEA4 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 |author=Adewumi O, Aflatoonian B, Ahrlund-Richter L, ''et al'' |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}}</ref>
After nearly ten years of research<ref>{{cite journal | author = Thomson J, Itskovitz-Eldor J, Shapiro S, Waknitz M, Swiergiel J, Marshall V, Jones J | title = Embryonic stem cell lines derived from human blastocysts. | journal = Science | volume = 282 | issue = 5391 | pages = 1145–7 | year = 1998 | pmid = 9804556 | doi = 10.1126/science.282.5391.1145}}</ref>, there are no approved treatments or human trials using embryonic stem cells. ES cells, being totipotent 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= |pages=4525–35 |year=2007 |pmid=17485394 |doi=10.2741/2407}}</ref> Many nations currently have [[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.
== Adult stem cells ==
{{main|Adult stem cell}}
[[Image:Stem cell division and differentiation.svg|thumb|160px|'''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]]
The term '''adult stem cell''' refers to any cell which is found in a developed organism that has two properties: the ability to divide and create another cell like itself and also divide and create a cell more differentiated than itself. Also known as '''[[somatic]]''' (from Greek Σωματικóς, "of the body") stem cells and '''germline''' (giving rise to gametes) stem cells, they can be found in children, as well as adults.<ref>{{cite journal |author=Jiang Y, Jahagirdar BN, Reinhardt RL, ''et al'' |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}}</ref>
Pluripotent adult stem cells are rare and generally small in number but can be found in a number of tissues including umbilical cord blood.<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> A great deal of adult stem cell research has focused on clarifying their capacity to divide or self-renew indefinitely and their differentiation potential.<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}}</ref> In mice, pluripotent stem cells are directly generated from adult fibroblast cultures.<ref>{{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]], 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>[http://www.ucsfhealth.org/childrens/medical_services/cancer/bmt/treatments/leukemia.html], 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://www.dvmnews.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 [[embryonic stem cell]]s, because the production of adult stem cells does not require the destruction of an [[embryo]]. Additionally, because in some instances adult stem cells can be obtained from the intended recipient, (an [[autograft]]) the risk of rejection is essentially non-existent in these situations. Consequently, more US government funding is being provided for adult stem cell research.<ref>[http://www.hhs.gov/news/press/2004pres/20040714b.html],USDHHS Stem Cell FAQ 2004</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 dpp and adherins 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}}</ref>
{{main|Induced Pluripotent Stem Cell}}
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>{{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> However, the need to transform these cells with an oncogene may prevent the use of this approach in therapy.
==Treatments==
{{main|Stem cell treatments}}
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]] 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}}</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.
Stem cells, however, are already used extensively in research, and some scientists do not see cell therapy as the first goal of the research, but see the investigation of stem cells as a goal worthy in itself.<ref>{{cite web | 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 | date=2006-08-14 | accessdate=2006-12-28}}</ref>
==Controversy surrounding human embryonic stem cell research==
{{main|Stem cell controversy}}
There exists a widespread controversy over human embryonic stem cell research that emanates from the techniques used in the creation and usage of stem cells. [[Embryonic stem cell|Human embryonic stem cell]] research is controversial because, with the present state of technology, starting a [[stem cell line]] requires the destruction of a [[embryo|human embryo]] and/or [[therapeutic cloning]]. However, recently, it has been shown in principle that adult stem cell lines can be manipulated to generate embryonic-like stem cell lines using a single-cell biopsy similar to that used in [[preimplantation genetic diagnosis]] that may allow stem cell creation without embryonic destruction.<ref>[http://www.npr.org/templates/story/story.php?storyId=5696557 Firm Creates Stem Cells Without Hurting Embryos : NPR<!-- Bot generated title -->]</ref> It is not the entire field of stem cell research, but the specific field of human embryonic stem cell research that is at the centre of an ethical debate.
Opponents of the research argue that embryonic stem cell technologies are a [[slippery slope]] to [[reproductive cloning]] and can fundamentally devalue human life. Those in the [[pro-life]] movement argue that a human embryo is a human life and is therefore entitled to protection.
Contrarily, supporters of embryonic stem cell research argue that such research should be pursued because the resultant treatments could have significant medical potential. It is also noted that excess embryos created for [[invitro fertilization|in vitro fertilization]] could be donated with consent and used for the research.
The ensuing debate has prompted authorities around the world to seek regulatory frameworks and highlighted the fact that stem cell research represents a [[social]] and [[ethical]] challenge.
==Key stem cell research events==
* '''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".
* '''1992''' - Neural stem cells are cultured ''[[in vitro]]'' as neurospheres.
* '''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]].
* '''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>[http://www.sciam.com/article.cfm?articleID=0008B8F9-AC62-1C75-9B81809EC588EF21&pageNumber=4&catID=4 The First Human Cloned Embryo: Scientific American<!-- Bot generated title -->]</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.
*'''August 2006''' - Rat '''[[Induced pluripotent stem cell]]s''': the journal [[Cell (journal)|''Cell'']] publishes Kazutoshi Takahashi and Shinya Yamanaka, [http://www.cell.com/content/article/fulltext?uid=PIIS0092867406009767 "Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors"].
*'''October 2006''' - Scientists in England create the first ever artificial liver cells using umbilical cord blood stem cells.<ref>[http://discovermagazine.com/2007/mar/good-news-for-alcoholics Good News for Alcoholics | Biotechnology | DISCOVER Magazine<!-- Bot generated title -->]</ref><ref>[http://news.scotsman.com/health.cfm?id=1608072006 Scotsman.com News<!-- Bot generated title -->]</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]].[http://www.nature.com/nbt/journal/v25/n1/abs/nbt1274.html] This may potentially provide an alternative to embryonic stem cells for use in research and therapy.<ref>[http://www.boston.com/news/local/massachusetts/articles/2007/01/07/amniotic_fluid_yields_stem_cells_harvard_researchers_report/ Amniotic fluid yields stem cells, Harvard researchers report - Boston.com<!-- Bot generated title -->]</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 <!--Retrieved from CrossRef by DOI bot-->}}</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 <!--Retrieved from CrossRef by DOI bot-->}}</ref>
*'''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
|accessdaymonth = 8 October|accessyear = 2007|publisher = Nobelprize.org}}</ref>
*'''November 2007''' - Human '''[[Induced pluripotent stem cell]]s''': Two similar papers released by their respective journals prior to formal publication: in [[Cell (journal)|''Cell'']] by [[Kazutoshi Takahashi]] and [[Shinya Yamanaka]], [http://images.cell.com/images/Edimages/Cell/IEPs/3661.pdf "Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors"], and in ''Science'' by Junying Yu, et al., from the research group of [[James Thomson (cell biologist)|James Thomson]], [http://www.sciencemag.org/cgi/content/abstract/1151526 "Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells"]: 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''' - Human embryonic stem cell lines were generated without destruction of the embryo<ref>[http://www.cellstemcell.com/content/article/abstract?uid=PIIS193459090700330X Cell Stem Cell - Chung et al<!-- Bot generated title -->]</ref>
*'''January 2008''' - Development of human cloned blastocysts following [[somatic cell nuclear transfer]] with adult fibroblasts<ref>http://stemcells.alphamedpress.org/cgi/reprint/2007-0252v1.pdf</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 previous 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>[http://www.ncbi.nlm.nih.gov/pubmed/18276851?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum Generation of Pluripotent Stem Cells from Adult Mo...[Science. 2008] - PubMed Result<!-- Bot generated title -->]</ref><ref>[http://blogs.nature.com/reports/theniche/2008/02/adult_cell_types_besides_skin.html The Niche: Adult cell types besides skin are reprogrammed<!-- Bot generated title -->]</ref>
==Stem cell funding & policy debate in the US==
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* '''1993''' - As per the National Institutes of Health Revitalization Act, Congress and President [[Bill Clinton]] give the NIH direct authority to fund human embryo research for the first time.<ref>[http://www.pbs.org/wgbh/nova/sciencenow/dispatches/050413.html Dispatches: The Politics of Stem Cells] [[PBS]]</ref>
* '''1995''' - The U.S. Congress enacts into law an appropriations bill attached to which is the [[Dickey Amendment]] which prohibited federally appropriated funds to be used for research where human embryos would be either created or destroyed. This predates the creation of the first human embryonic stem cell lines.
* '''1999''' - After the creation of the first human embryonic stem cell lines in 1998 by James Thomson of the University of Wisconsin, Harriet Rabb, the top lawyer at the Department of Health and Human Services, releases a legal opinion that would set the course for Clinton Administration policy. Federal funds, obviously, could not be used to derive stem cell lines (because derivation involves embryo destruction). However, she concludes that because human embryonic stem cells "are not a human embryo within the statutory definition," the Dickey-Wicker Amendment does not apply to them. The NIH was therefore free to give federal funding to experiments involving the cells themselves. President Clinton strongly endorses the new guidelines, noting that human embryonic stem cell research promised "potentially staggering benefits." And with the guidelines in place, the NIH begins accepting grant proposals from scientists.<ref>[http://www.pbs.org/wgbh/nova/sciencenow/dispatches/050413.html Dispatches: The Politics of Stem Cells] [[PBS]]</ref>
* '''02 November, 2004''' - [[California]] voters approve [[Proposition 71]], which provides $3 billion in state funds over ten years to human embryonic stem cell research.
* '''2001-2006''' - U.S. [[President]] [[George W. Bush]] signs an executive order which restricts federally-funded stem cell research on embryonic stem cells to the already derived cell lines. He supports federal funding for embryonic stem cell research on the already existing lines of approximately $100 million and $250 million for research on adult and animal stem cells.
* '''5 May, 2006''' - Senator [[Rick Santorum]] introduces bill number S. 2754, or the Alternative Pluripotent Stem Cell Therapies Enhancement Act, into the [[United States Senate|U.S. Senate]].
* '''18 July, 2006''' - The U.S. Senate passes the Stem Cell Research Enhancement Act H.R. 810 and votes down Senator Santorum's S. 2754.
* '''19 July, 2006''' - [[President]] [[George W. Bush]] vetoes H.R. 810 ([[Stem Cell Research Enhancement Act]]), a bill that would have reversed the Gingrich-era appropriations amendment which made it illegal for federal money to be used for research where stem cells are derived from the destruction of an embryo.
* '''07 November, 2006''' - The people of the U.S. state of [[Missouri]] passed [[Missouri Constitutional Amendment 2 (2006)|Amendment 2]], which allows usage of any stem cell research and therapy allowed under federal law, but prohibits human reproductive cloning.<ref>[http://www.sos.mo.gov/elections/2006petitions/ppStemCell.asp Full-text of Missouri Constitution Amendment 2]</ref>
*'''16 February, 2007''' – The California Institute for Regenerative Medicine became the biggest financial backer of human embryonic stem cell research in the United States when they awarded nearly $45 million in research grants.<ref>[http://www.cbsnews.com/stories/2007/02/17/ap/national/mainD8NB4T002.shtml Calif. Awards $45M in Stem Cell Grants] [[Associated Press]], Feb. 17, 2007.</ref>
==See also==
*[[The American Society for Cell Biology]]
*[[California Institute for Regenerative Medicine]]
*[[Genetics Policy Institute]]
*[[Cancer stem cells]]
*[[Induced Pluripotent Stem Cell]] (iPS Cell)
*[[Odontis]]
*[[Meristem]]
==References==
{{reflist|2}}
==External links==
<!-- 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://www.tellmeaboutstemcells.org/ Tell Me About Stem Cells: Quick and simple guide explaining the science behind stem cells]
*[http://stemcells.nih.gov/info/basics/ Stem Cell Basics]
*[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.sciam.com/article.cfm?chanID=sa006&articleID=000DFA43-04B1-10AA-84B183414B7F0000 Scientific American Magazine (June 2004 Issue) The Stem Cell Challenge]
*[http://www.sciam.com/article.cfm?chanID=sa006&articleID=000B1BED-0C0A-1498-8C0A83414B7F0000 Scientific American Magazine (July 2006 Issue) Stem Cells: The Real Culprits in Cancer?]
*[http://stemcells.nih.gov/ National Institutes of Health]
*[http://www.scrfi.org Stem Cell Research Forum of India ]
*{{sep entry|stem-cells|Ethics of Stem Cell Research|Andrew Siegel}}
;Peer-reviewed journals
*[http://www.stemcells.com STEM CELLS®]
*[http://www.tandf.co.uk/journals/titles/14653249.asp Cytotherapy]
*[http://www.liebertpub.com/publication.aspx?pub_id=9 Cloning and Stem Cells]
*[http://www.liebertpub.com/publication.aspx?pub_id=125 Stem Cells and Development]
*[http://www.futuremedicine.com/loi/rme Regenerative Medicine]
*[http://www.nature.com/nbt/journal/v25/n1/abs/nbt1274.html Isolation of amniotic stem cell lines with potential for therapy]
{{Stem cells}}
{{embryology}}
[[Category:Stem cells| ]]
[[Category:Biotechnology]]
[[Category:Cell biology]]
[[Category:Developmental biology]]
[[Category:Cloning]]
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