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Embryoid body
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== Background == The pluripotent cell types that comprise embryoid bodies include [[embryonic stem cells]] (ESCs) derived from the [[blastocyst]] stage of embryos from mouse (mESC),<ref>{{Cite journal | last1 = Martin | first1 = G. R. | title = Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 78 | issue = 12 | pages = 7634β7638 | year = 1981 | pmid = 6950406 | pmc = 349323 | doi=10.1073/pnas.78.12.7634 | bibcode = 1981PNAS...78.7634M | doi-access = free }}</ref><ref>{{Cite journal | last1 = Evans | first1 = M. J. | last2 = Kaufman | first2 = M. H. | title = Establishment in culture of pluripotential cells from mouse embryos | journal = Nature | volume = 292 | issue = 5819 | pages = 154β156 | year = 1981 | pmid = 7242681 | doi=10.1038/292154a0 | bibcode = 1981Natur.292..154E | s2cid = 4256553 }}</ref> primate,<ref>{{Cite journal | last1 = Thomson | first1 = J. A. | last2 = Kalishman | first2 = J. | last3 = Golos | first3 = T. G. | last4 = Durning | first4 = M. | last5 = Harris | first5 = C. P. | last6 = Becker | first6 = R. A. | last7 = Hearn | first7 = J. P. | title = Isolation of a primate embryonic stem cell line | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 17 | pages = 7844β7848 | year = 1995 | pmid = 7544005 | pmc = 41242 | doi=10.1073/pnas.92.17.7844 | bibcode = 1995PNAS...92.7844T | doi-access = free }}</ref> and human (hESC)<ref>{{Cite journal | last1 = Thomson | first1 = J. A. | last2 = Itskovitz-Eldor | first2 = J. | last3 = Shapiro | first3 = S. S. | last4 = Waknitz | first4 = M. A. | last5 = Swiergiel | first5 = J. J. | last6 = Marshall | first6 = V. S. | last7 = Jones | first7 = J. M. | title = Embryonic stem cell lines derived from human blastocysts | journal = Science | volume = 282 | issue = 5391 | pages = 1145β1147 | year = 1998 | pmid = 9804556 | doi=10.1126/science.282.5391.1145 | bibcode = 1998Sci...282.1145T | doi-access = free }}</ref> sources. Additionally, EBs can be formed from embryonic stem cells derived through alternative techniques, including [[somatic cell nuclear transfer]]<ref>{{Cite journal | last1 = Briggs | first1 = R. | last2 = King | first2 = T. J. | title = Transplantation of Living Nuclei from Blastula Cells into Enucleated Frogs' Eggs | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 38 | issue = 5 | pages = 455β463 | year = 1952 | pmid = 16589125 | pmc = 1063586 | doi=10.1073/pnas.38.5.455 | bibcode = 1952PNAS...38..455B | doi-access = free }}</ref><ref>{{Cite journal | last1 = Wilmut | first1 = I. | authorlink1 = Ian Wilmut | last2 = Schnieke | first2 = A. E. | last3 = McWhir | first3 = J. | last4 = Kind | first4 = A. J. | last5 = Campbell | first5 = K. H. S. | authorlink5 = Keith Campbell (biologist) | title = Viable offspring derived from fetal and adult mammalian cells | doi = 10.1038/385810a0 | journal = Nature | volume = 385 | issue = 6619 | pages = 810β813 | year = 1997 | pmid = 9039911 | pmc = | bibcode = 1997Natur.385..810W | s2cid = 4260518 }}</ref><ref>{{Cite journal | last1 = Munsie | first1 = M. J. | last2 = Michalska | first2 = A. E. | last3 = O'Brien | first3 = C. M. | last4 = Trounson | first4 = A. O. | last5 = Pera | first5 = M. F. | last6 = Mountford | first6 = P. S. | title = Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei | journal = Current Biology | volume = 10 | issue = 16 | pages = 989β992 | year = 2000 | pmid = 10985386 | doi=10.1016/s0960-9822(00)00648-5 | doi-access = free | bibcode = 2000CBio...10..989M }}</ref> or the reprogramming of somatic cells to yield [[induced pluripotent stem cells]] (iPS).<ref>{{Cite journal | last1 = Takahashi | first1 = K. | last2 = Yamanaka | first2 = S. | authorlink2 = Shinya Yamanaka | title = Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors | journal = Cell | volume = 126 | issue = 4 | pages = 663β76 | year = 2006 | pmid = 16904174 | doi = 10.1016/j.cell.2006.07.024 | hdl = 2433/159777 | s2cid = 1565219 | hdl-access = free }}</ref><ref>{{Cite journal | last1 = Takahashi | first1 = K. | last2 = Tanabe | first2 = K. | last3 = Ohnuki | first3 = M. | last4 = Narita | first4 = M. | last5 = Ichisaka | first5 = T. | last6 = Tomoda | first6 = K. | last7 = Yamanaka | first7 = S. | authorlink7 = Shinya Yamanaka | doi = 10.1016/j.cell.2007.11.019 | title = Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors | journal = Cell | volume = 131 | issue = 5 | pages = 861β872 | year = 2007 | pmid = 18035408 | pmc = | hdl = 2433/49782 | s2cid = 8531539 | hdl-access = free }}</ref><ref>{{Cite journal | last1 = Yu | first1 = J. | last2 = Vodyanik | first2 = M. A. | last3 = Smuga-Otto | first3 = K. | last4 = Antosiewicz-Bourget | first4 = J. | last5 = Frane | first5 = J. L. | last6 = Tian | first6 = S. | last7 = Nie | first7 = J. | last8 = Jonsdottir | first8 = G. A. | last9 = Ruotti | first9 = V. | last10 = Stewart | doi = 10.1126/science.1151526 | first10 = R. | last11 = Slukvin | first11 = I. I. | last12 = Thomson | first12 = J. A. | title = Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells | journal = Science | volume = 318 | issue = 5858 | pages = 1917β1920 | year = 2007 | pmid = 18029452 | pmc = | bibcode = 2007Sci...318.1917Y | s2cid = 86129154 }}</ref><ref>{{Cite journal | last1 = Park | first1 = I. H. | last2 = Arora | first2 = N. | last3 = Huo | first3 = H. | last4 = Maherali | first4 = N. | last5 = Ahfeldt | first5 = T. | last6 = Shimamura | first6 = A. | last7 = Lensch | first7 = M. W. | last8 = Cowan | first8 = C. | last9 = Hochedlinger | first9 = K. | doi = 10.1016/j.cell.2008.07.041 | last10 = Daley | first10 = G. Q. | title = Disease-Specific Induced Pluripotent Stem Cells | journal = Cell | volume = 134 | issue = 5 | pages = 877β886 | year = 2008 | pmid = 18691744 | pmc =2633781 }}</ref> Similar to ESCs [[cell culture|cultured in monolayer]] formats, ESCs within embryoid bodies undergo differentiation and cell specification along the three [[germ layer|germ lineages]] β endoderm, [[ectoderm]], and mesoderm β which comprise all [[somatic (biology)|somatic]] cell types.<ref>{{Cite journal | last1 = Itskovitz-Eldor | first1 = J. | last2 = Schuldiner | first2 = M. | last3 = Karsenti | first3 = D. | last4 = Eden | first4 = A. | last5 = Yanuka | first5 = O. | last6 = Amit | first6 = M. | last7 = Soreq | first7 = H. | last8 = Benvenisty | first8 = N. | title = Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers | journal = Molecular Medicine | volume = 6 | issue = 2 | pages = 88β95 | year = 2000 | doi = 10.1007/BF03401776 | pmid = 10859025 | pmc = 1949933 }}</ref><ref name="ReferenceA">{{Cite journal | last1 = Doetschman | first1 = T. C. | last2 = Eistetter | first2 = H. | last3 = Katz | first3 = M. | last4 = Schmidt | first4 = W. | last5 = Kemler | first5 = R. | title = The in vitro development of blastocyst-derived embryonic stem cell lines: Formation of visceral yolk sac, blood islands and myocardium | journal = Journal of Embryology and Experimental Morphology | volume = 87 | pages = 27β45 | year = 1985 | pmid = 3897439 }}</ref> In contrast to monolayer cultures, however, the spheroid structures that are formed when ESCs aggregate enables the non-adherent culture of EBs in suspension, making EB cultures inherently scalable, which is useful for bioprocessing approaches, whereby large yields of cells can be produced for potential clinical applications.<ref>{{Cite journal | last1 = Dang | first1 = S. M. | last2 = Gerecht-Nir | first2 = S. | last3 = Chen | first3 = J. | last4 = Itskovitz-Eldor | first4 = J. | last5 = Zandstra | first5 = P. W. | title = Controlled, Scalable Embryonic Stem Cell Differentiation Culture | doi = 10.1634/stemcells.22-3-275 | journal = Stem Cells | volume = 22 | issue = 3 | pages = 275β282 | year = 2004 | pmid = 15153605 | pmc = | doi-access = free }}</ref> Additionally, although EBs largely exhibit heterogeneous patterns of differentiated cell types, ESCs are capable of responding to similar cues that direct [[embryogenesis|embryonic development]].<ref name="ReferenceB">{{Cite journal | last1 = Murry | first1 = C. E. | last2 = Keller | first2 = G. | doi = 10.1016/j.cell.2008.02.008 | title = Differentiation of Embryonic Stem Cells to Clinically Relevant Populations: Lessons from Embryonic Development | journal = Cell | volume = 132 | issue = 4 | pages = 661β680 | year = 2008 | pmid = 18295582 | pmc = | doi-access = free }}</ref> Therefore, the three-dimensional structure, including the establishment of complex [[cell adhesion]]s and paracrine [[cell signaling|signaling]] within the EB microenvironment,<ref name="ReferenceC">{{Cite journal | last1 = Bratt-Leal | first1 = A. S. M. | last2 = Carpenedo | first2 = R. L. | last3 = McDevitt | first3 = T. C. | doi = 10.1002/btpr.139 | title = Engineering the embryoid body microenvironment to direct embryonic stem cell differentiation | journal = Biotechnology Progress | volume = 25 | issue = 1 | pages = 43β51 | year = 2009 | pmid = 19198003 | pmc =2693014 }}</ref> enables differentiation and [[morphogenesis]] which yields microtissues that are similar to native tissue structures. Such microtissues are promising to directly<ref name="ReferenceB"/> or indirectly<ref>{{Cite journal | last1 = Nair | first1 = R. | last2 = Shukla | first2 = S. | last3 = McDevitt | first3 = T. C. | doi = 10.1002/jbm.a.31851 | title = Acellular matrices derived from differentiating embryonic stem cells | journal = Journal of Biomedical Materials Research Part A | volume = 87A | issue = 4 | pages = 1075β1085 | year = 2008 | pmid = 18260134 | pmc = | hdl = 1853/37170 | hdl-access = free }}</ref><ref>{{Cite journal | last1 = Baraniak | first1 = P. R. | last2 = McDevitt | first2 = T. C. | doi = 10.2217/rme.09.74 | title = Stem cell paracrine actions and tissue regeneration | journal = Regenerative Medicine | volume = 5 | issue = 1 | pages = 121β143 | year = 2010 | pmid = 20017699 | pmc =2833273 }}</ref> repair damaged or diseased tissue in regenerative medicine applications, as well as for in vitro testing in the pharmaceutical industry and as a model of embryonic development.
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