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Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice

Nat Med. 2016 Mar;22(3):306-11. doi: 10.1038/nm.4030. Epub 2016 Jan 25.

Vegas AJ1,2, Veiseh O1,2,3, Gürtler M4, Millman JR4, Pagliuca FW4, Bader AR1,2, Doloff JC1,2, Li J1,2, Chen M1,2, Olejnik K1,2, Tam HH1,2,3, Jhunjhunwala S1,2, Langan E1,2, Aresta-Dasilva S1,2, Gandham S1,2, McGarrigle JJ5, Bochenek MA5, Hollister-Lock J6, Oberholzer J5, Greiner DL7, Weir GC6, Melton DA4,8, Langer R1,2,3,9,10, Anderson DG1,2,3,9,10.

Abstract

The 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.

PMID 26808346

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License Number 3824450755291 License date Mar 08, 2016 Licensed content publisher Nature Publishing Group Licensed content publication Nature Medicine Licensed content title Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice Licensed content author Arturo J Vegas, Omid Veiseh, Mads Gürtler, Jeffrey R Millman, Felicia W Pagliuca, Andrew R Bader Licensed content date Jan 25, 2016 Volume number 22 Issue number 3 Type of Use post on a website Requestor type academic/university or research institute Format electronic Portion figures/tables/illustrations Number of figures/tables/illustrations 2 High-res required no Figures Figure 1 and 3 Author of this NPG article no Your reference number None Homepage URL for posting content https://embryology.med.unsw.edu.au/ Name of internet owner Mark Hill Expected posting date Feb 2016