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dc.contributor.authorGürtler, Mads
dc.contributor.authorMillman, Jeffrey R
dc.contributor.authorPagliuca, Felicia W
dc.contributor.authorMcGarrigle, James J
dc.contributor.authorBochenek, Matthew A
dc.contributor.authorHollister-Lock, Jennifer
dc.contributor.authorOberholzer, Jose
dc.contributor.authorGreiner, Dale L
dc.contributor.authorWeir, Gordon C
dc.contributor.authorMelton, Douglas A
dc.contributor.authorVegas, Arturo
dc.contributor.authorVeiseh, Omid
dc.contributor.authorBader, Andrew
dc.contributor.authorDoloff, Joshua C
dc.contributor.authorLi, Jie
dc.contributor.authorChen, Michael
dc.contributor.authorOlejnik, Karsten
dc.contributor.authorTam, Hok Hei
dc.contributor.authorJhunjhunwala, Siddharth
dc.contributor.authorLangan, Erin
dc.contributor.authorAresta-Dasilva, Stephanie K
dc.contributor.authorGandham, Srujan Kumar
dc.contributor.authorLanger, Robert S
dc.contributor.authorAnderson, Daniel Griffith
dc.date.accessioned2017-02-15T20:16:15Z
dc.date.available2017-02-15T20:16:15Z
dc.date.issued2016-01
dc.date.submitted2015-10
dc.identifier.issn1078-8956
dc.identifier.issn1546-170X
dc.identifier.urihttp://hdl.handle.net/1721.1/106945
dc.description.abstractThe transplantation of glucose-responsive, insulin-producing cells offers the potential for restoring glycemic control in individuals with diabetes. Pancreas transplantation and the infusion of cadaveric islets are currently implemented clinically, but these approaches are limited by the adverse effects of immunosuppressive therapy over the lifetime of the recipient and the limited supply of donor tissue. The latter concern may be addressed by recently described glucose-responsive mature beta cells that are derived from human embryonic stem cells (referred to as SC-β cells), which may represent an unlimited source of human cells for pancreas replacement therapy. Strategies to address the immunosuppression concerns include immunoisolation of insulin-producing cells with porous biomaterials that function as an immune barrier. However, clinical implementation has been challenging because of host immune responses to the implant materials. Here we report the first long-term glycemic correction of a diabetic, immunocompetent animal model using human SC-β cells. SC-β cells were encapsulated with alginate derivatives capable of mitigating foreign-body responses in vivo and implanted into the intraperitoneal space of C57BL/6J mice treated with streptozotocin, which is an animal model for chemically induced type 1 diabetes. These implants induced glycemic correction without any immunosuppression until their removal at 174 d after implantation. Human C-peptide concentrations and in vivo glucose responsiveness demonstrated therapeutically relevant glycemic control. Implants retrieved after 174 d contained viable insulin-producing cells.en_US
dc.description.sponsorshipLeona M. and Harry B. Helmsley Charitable Trust (Grant 3-SRA-2014-285-M-R)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grants EB000244, EB000351, DE013023, and CA151884)en_US
dc.description.sponsorshipTayebati Family Foundationen_US
dc.description.sponsorshipUnited States. Dept. of Defense. Congressionally Directed Medical Research Programs (Grant W81XWH-13-1-0215)en_US
dc.description.sponsorshipJuvenile Diabetes Research Foundation International (Grant 3-2013-178)en_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/nm.4030en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePMCen_US
dc.titleLong-term glycemic control using polymer-encapsulated human stem cell–derived beta cells in immune-competent miceen_US
dc.typeArticleen_US
dc.identifier.citationVegas, Arturo J et al. “Long-Term Glycemic Control Using Polymer-Encapsulated Human Stem Cell–derived Beta Cells in Immune-Competent Mice.” Nature Medicine 22.3 (2016): 306–311.en_US
dc.contributor.departmentInstitute for Medical Engineering and Scienceen_US
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Mechanical Engineeringen_US
dc.contributor.mitauthorVegas, Arturo
dc.contributor.mitauthorVeiseh, Omid
dc.contributor.mitauthorBader, Andrew
dc.contributor.mitauthorDoloff, Joshua C
dc.contributor.mitauthorLi, Jie
dc.contributor.mitauthorChen, Michael
dc.contributor.mitauthorOlejnik, Karsten
dc.contributor.mitauthorTam, Hok Hei
dc.contributor.mitauthorJhunjhunwala, Siddharth
dc.contributor.mitauthorLangan, Erin
dc.contributor.mitauthorAresta-Dasilva, Stephanie K
dc.contributor.mitauthorGandham, Srujan Kumar
dc.contributor.mitauthorLanger, Robert S
dc.contributor.mitauthorAnderson, Daniel Griffith
dc.relation.journalNature Medicineen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsVegas, Arturo J; Veiseh, Omid; Gürtler, Mads; Millman, Jeffrey R; Pagliuca, Felicia W; Bader, Andrew R; Doloff, Joshua C; Li, Jie; Chen, Michael; Olejnik, Karsten; Tam, Hok Hei; Jhunjhunwala, Siddharth; Langan, Erin; Aresta-Dasilva, Stephanie; Gandham, Srujan; McGarrigle, James J; Bochenek, Matthew A; Hollister-Lock, Jennifer; Oberholzer, Jose; Greiner, Dale L; Weir, Gordon C; Melton, Douglas A; Langer, Robert; Anderson, Daniel Gen_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-9522-8208
dc.identifier.orcidhttps://orcid.org/0000-0001-8223-035X
dc.identifier.orcidhttps://orcid.org/0000-0002-4323-3264
dc.identifier.orcidhttps://orcid.org/0000-0002-5840-2366
dc.identifier.orcidhttps://orcid.org/0000-0002-4680-3832
dc.identifier.orcidhttps://orcid.org/0000-0002-2358-0330
dc.identifier.orcidhttps://orcid.org/0000-0001-8046-2288
dc.identifier.orcidhttps://orcid.org/0000-0003-1520-4180
dc.identifier.orcidhttps://orcid.org/0000-0003-4255-0492
dc.identifier.orcidhttps://orcid.org/0000-0001-5629-4798
mit.licensePUBLISHER_POLICYen_US


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