Editing Stem cell (section)

==Induced pluripotent==
{{Main|Induced pluripotent stem cell}}

Adult stem cells have limitations with their potency; unlike [[embryonic stem cell]]s (ESCs), they are not able to differentiate into cells from all three [[germ layers]]. As such, they are deemed [[cell potency|multipotent]].

However, [[reprogramming]] allows for the creation of pluripotent cells, [[induced pluripotent stem cell]]s (iPSCs), from adult cells. These are not adult stem cells, but somatic cells (e.g. epithelial cells) reprogrammed to give rise to cells with pluripotent capabilities. Using genetic reprogramming with protein [[transcription factors]], pluripotent stem cells with ESC-like capabilities have been derived.<ref name="Economist2007_11_22">{{cite news|title=Making human embryonic stem cells|newspaper=The Economist|url=http://www.economist.com/science/displaystory.cfm?story_id=10170972|date=2007-11-22}}</ref><ref>{{cite web|url=https://www.npr.org/templates/story/story.php?storyId=16466265|publisher=[[National Public Radio]]|title=Skin Cells Can Become Embryonic Stem Cells| last1 = Brand | first1 = Madeleine | last2 = Palca | first2 = Joe | last3 = Cohen | first3 = Alex | name-list-style = vanc |date=2007-11-20}}</ref><ref>{{cite web|url=https://www.pbs.org/newshour/bb/science/july-dec07/stemcells_11-20.html|title=Breakthrough Set to Radically Change Stem Cell Debate|publisher=[[News Hour with Jim Lehrer]]|date=2007-11-20|access-date=2017-09-15|archive-date=2014-01-22|archive-url=https://web.archive.org/web/20140122092539/http://www.pbs.org/newshour/bb/science/july-dec07/stemcells_11-20.html|url-status=dead}}</ref> The first demonstration of induced pluripotent stem cells was conducted by [[Shinya Yamanaka]] and his colleagues at [[Kyoto University]].<ref name = "overview">{{cite journal | vauthors = Kimbrel EA, Lanza R | title = Pluripotent stem cells: the last 10 years | journal = Regenerative Medicine | volume = 11 | issue = 8 | pages = 831–847 | date = December 2016 | pmid = 27908220 | doi = 10.2217/rme-2016-0117 | doi-access = free }}</ref> They used the transcription factors [[Oct-4|Oct3/4]], [[Sox2]], [[c-Myc]], and [[Klf4]] to reprogram mouse fibroblast cells into pluripotent cells.<ref name="Economist2007_11_22"/><ref name= "og Yak">{{cite journal | vauthors = Takahashi K, Yamanaka S | title = Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors | journal = Cell | volume = 126 | issue = 4 | pages = 663–676 | date = August 2006 | pmid = 16904174 | doi = 10.1016/j.cell.2006.07.024 | hdl = 2433/159777 | s2cid = 1565219 | hdl-access = free }}</ref> Subsequent work used these factors to induce pluripotency in human fibroblast cells.<ref name= "2007 Yak">{{cite journal | vauthors = Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S | title = Induction of pluripotent stem cells from adult human fibroblasts by defined factors | journal = Cell | volume = 131 | issue = 5 | pages = 861–872 | date = November 2007 | pmid = 18035408 | doi = 10.1016/j.cell.2007.11.019 | hdl = 2433/49782 | s2cid = 8531539 | hdl-access = free }}</ref> [[Junying Yu]], [[James Thomson (cell biologist)|James Thomson]], and their colleagues at the [[University of Wisconsin–Madison]] used a different set of factors, Oct4, Sox2, Nanog and Lin28, and carried out their experiments using cells from human [[foreskin]].<ref name="Economist2007_11_22"/><ref name = "wisconsin">{{cite journal | vauthors = Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA | title = Induced pluripotent stem cell lines derived from human somatic cells | journal = Science | volume = 318 | issue = 5858 | pages = 1917–1920 | date = December 2007 | pmid = 18029452 | doi = 10.1126/science.1151526 | bibcode = 2007Sci...318.1917Y | s2cid = 86129154 }}</ref> However, they were able to replicate [[Yamanaka]]'s finding that inducing pluripotency in human cells was possible.

Induced pluripotent stem cells differ from embryonic stem cells. They share many similar properties, such as [[pluripotency]] and differentiation potential, the expression of [[pluripotency]] genes, [[epigenetic]] patterns, [[embryoid body]] and [[teratoma]] formation, and viable [[chimera (genetics)|chimera]] formation,<ref name="overview" /><ref name = "og Yak" /> but there are many differences within these properties. The chromatin of iPSCs appears to be more "closed" or methylated than that of ESCs.<ref name="overview" /><ref name = "og Yak" /> Similarly, the gene expression pattern between ESCs and iPSCs, or even iPSCs sourced from different origins.<ref name="overview" /> There are thus questions about the "completeness" of [[reprogramming]] and the somatic memory of induced pluripotent stem cells. Despite this, inducing somatic cells to be pluripotent appears to be viable.

As a result of the success of these experiments, [[Ian Wilmut]], who helped create the first cloned animal [[Dolly the Sheep]], has announced that he will abandon [[somatic cell nuclear transfer]] as an avenue of research.<ref>"His inspiration comes from the research by Prof [[Shinya Yamanaka]] at [[Kyoto University]], which suggests a way to create human embryo stem cells without the need for human eggs, which are in extremely short supply, and without the need to create and destroy human cloned embryos, which is bitterly opposed by the pro life movement." {{cite news|url=https://www.telegraph.co.uk/science/science-news/3314696/Dolly-creator-Prof-Ian-Wilmut-shuns-cloning.html|archive-url=https://web.archive.org/web/20090730031336/http://www.telegraph.co.uk/science/science-news/3314696/Dolly-creator-Prof-Ian-Wilmut-shuns-cloning.html|archive-date=2009-07-30|title=Dolly creator Prof Ian Wilmut shuns cloning| last = Highfield | first = Roger | name-list-style = vanc |date=2007-11-16|newspaper=[[The Daily Telegraph|The Telegraph]] | location=London}}</ref>

The ability to induce pluripotency benefits developments in [[tissue engineering]]. By providing a suitable scaffold and microenvironment, iPSC can be differentiated into cells of therapeutic application, and for ''in vitro'' models to study toxins and pathogenesis.<ref>{{cite journal |vauthors=Maldonado M, Luu RJ, Ico G, Ospina A, Myung D, Shih HP, Nam J |date=September 2017 |title=Lineage- and developmental stage-specific mechanomodulation of induced pluripotent stem cell differentiation |journal=Stem Cell Research & Therapy |volume=8 |issue=1 |pages=216 |doi=10.1186/s13287-017-0667-2 |pmc=5622562 |pmid=28962663 |doi-access=free}}</ref>

Induced pluripotent stem cells provide several therapeutic advantages. Like ESCs, they are [[pluripotent]]. They thus have great differentiation potential; theoretically, they could produce any cell within the human body (if [[reprogramming]] to pluripotency was "complete").<ref name = "overview" /> Moreover, unlike ESCs, they potentially could allow doctors to create a pluripotent stem cell line for each individual patient.<ref name="R&D">{{cite journal |first1=DA |last1=Robinton |author-link1=Daisy A. Robinton |first2=GQ |last2=Daley | title = The promise of induced pluripotent stem cells in research and therapy | journal = Nature | volume = 481 | issue = 7381 | pages = 295–305 | date = January 2012 | pmid = 22258608 | pmc = 3652331 | doi = 10.1038/nature10761 | bibcode = 2012Natur.481..295R }}</ref> Frozen blood samples can be used as a valuable source of induced pluripotent stem cells.<ref name="pmid20621045">{{cite journal | vauthors = Staerk J, Dawlaty MM, Gao Q, Maetzel D, Hanna J, Sommer CA, Mostoslavsky G, Jaenisch R | title = Reprogramming of human peripheral blood cells to induced pluripotent stem cells | journal = Cell Stem Cell | volume = 7 | issue = 1 | pages = 20–24 | date = July 2010 | pmid = 20621045 | pmc = 2917234 | doi = 10.1016/j.stem.2010.06.002}}
*{{lay source |template=cite news |date=2010-07-01 |title=Frozen blood a source of stem cells, study finds |url=http://www.newsdaily.com/stories/tre6604si-us-stemcells-frozen |archive-url=https://web.archive.org/web/20100703175036/http://www.newsdaily.com/stories/tre6604si-us-stemcells-frozen/ |archive-date=2010-07-03 |work=NewsDaily |agency=Reuters}}</ref>  Patient specific stem cells allow for the screening for side effects before drug treatment, as well as the reduced risk of transplantation rejection.<ref name= "R&D" /> Despite their current limited use therapeutically, iPSCs hold great potential for future use in medical treatment and research.

=== Cell cycle control ===
The key factors controlling the cell cycle also regulate [[pluripotency]]. Thus, manipulation of relevant genes can maintain pluripotency and reprogram somatic cells to an induced pluripotent state.<ref name=":2" /> However, reprogramming of somatic cells is often low in efficiency and considered [[stochastic]].<ref>{{cite journal | vauthors = Chen X, Hartman A, Guo S | title = Choosing Cell Fate Through a Dynamic Cell Cycle | journal = Current Stem Cell Reports | volume = 1 | issue = 3 | pages = 129–138 | date = 2015-09-01 | pmid = 28725536 | pmc = 5487535 | doi = 10.1007/s40778-015-0018-0 }}</ref>

With the idea that a more rapid cell cycle is a key component of pluripotency, reprogramming efficiency can be improved. Methods for improving pluripotency through manipulation of cell cycle regulators include: overexpression of Cyclin D/Cdk4, phosphorylation of [[SOX2|Sox2]] at S39 and S253, overexpression of Cyclin A and Cyclin E, knockdown of Rb, and knockdown of members of the [[CIP/KIP|Cip/Kip]] family or the Ink family.<ref name=":2" /> Furthermore, reprogramming efficiency is correlated with the number of cell divisions happened during the stochastic phase, which is suggested by the growing inefficiency of reprogramming of older or slow diving cells.<ref>{{cite journal | vauthors = Hindley C, Philpott A | title = The cell cycle and pluripotency | journal = The Biochemical Journal | volume = 451 | issue = 2 | pages = 135–143 | date = April 2013 | pmid = 23535166 | pmc = 3631102 | doi = 10.1042/BJ20121627 }}</ref>