Long term Glycemic Control Using Polymer Encapsulated, Human Stem-Cell Derived β-cells in Immune Competent mice

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Long term Glycemic Control Using Polymer Encapsulated, Human Stem-Cell Derived β-cells in Immune Competent mice

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Title: Long term Glycemic Control Using Polymer Encapsulated, Human Stem-Cell Derived β-cells in Immune Competent mice
Author: Vegas, 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; Bochenek, Matthew A.; Hollister-Lock, Jennifer; Oberholzer, Jose; Greiner, Dale L.; Weir, Gordon C.; Melton, Douglas A.; Langer, Robert; Anderson, Daniel G.

Note: Order does not necessarily reflect citation order of authors.

Citation: Vegas, A. J., O. Veiseh, M. Gürtler, J. R. Millman, F. W. Pagliuca, A. R. Bader, J. C. Doloff, et al. 2016. “Long term Glycemic Control Using Polymer Encapsulated, Human Stem-Cell Derived β-cells in Immune Competent mice.” Nature medicine 22 (3): 306-311. doi:10.1038/nm.4030. http://dx.doi.org/10.1038/nm.4030.
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Abstract: The transplantation of glucose-responsive, insulin-producing cells offers the potential for restoring glycemic control in diabetic patients1. Pancreas transplantation and the infusion of cadaveric islets are currently implemented clinically2, but are limited by the adverse effects of lifetime immunosuppression and the limited supply of donor tissue3. The latter concern may be addressed by recently described glucose responsive mature β-cells derived from human embryonic stem cells; called SC-β, these cells may represent an unlimited human cell source for pancreas replacement therapy4. Strategies to address the immunosuppression concern include immunoisolation of insulin-producing cells with porous biomaterials that function as an immune barrier5,6. However, clinical implementation has been challenging due to host immune responses to implant materials7. Here, we report the first long term glycemic correction of a diabetic, immune-competent animal model with 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 (IP) space of streptozotocin-treated (STZ) C57BL/6J mice. These implants induced glycemic correction until removal at 174 days without any immunosuppression. Human C-peptide concentrations and in vivo glucose responsiveness demonstrate therapeutically relevant glycemic control. Implants retrieved after 174 days contained viable insulin-producing cells.
Published Version: doi:10.1038/nm.4030
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825868/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:27822292
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