Long-term glycemic control using polymer-encapsulated human stem cell–derived beta cells in immune-competent mice
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Anderson_Long term glycemic.pdf
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Author(s)
Gürtler, Mads
Millman, Jeffrey R
Pagliuca, Felicia W
McGarrigle, James J
Bochenek, Matthew A
Hollister-Lock, Jennifer
Oberholzer, Jose
Greiner, Dale L
Weir, Gordon C
Melton, Douglas A
Date Issued
January 2016
Journal
Nature Medicine
Publisher
Nature Publishing Group
Citation
Vegas, 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.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article 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.
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DOI of Published Version
https://doi.org/10.1038/nm.4030
