2016 Long-term glycemic control using polymer-encapsulated human stem cell–derived beta cells in immune-competent mice
<p>Jan 16, 2018 05:22 PM</p>
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Nature Medicine </p>
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Arturo Vega</p>
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The transplantation of glucose-responsive, insulin-producing cells offers the potential for restoring glycemic control in individuals with diabetes<sup ><a id="ref-link-abstract-1" title="Robertson, R.P. Islet transplantation as a treatment for diabetes—a work in progress. N. Engl. J. Med. 350, 694–705 (2004)." href="https://www.nature.com/articles/nm.4030#ref1" >1</a></sup>. Pancreas transplantation and the infusion of cadaveric islets are currently implemented clinically<sup ><a id="ref-link-abstract-2" title="Shapiro, A.M. et al. International trial of the Edmonton protocol for islet transplantation. N. Engl. J. Med. 355, 1318–1330 (2006)." href="https://www.nature.com/articles/nm.4030#ref2" >2</a></sup>, 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<sup ><a id="ref-link-abstract-3" title="Hirshberg, B. Lessons learned from the international trial of the Edmonton protocol for islet transplantation. Curr. Diab. Rep. 7, 301–303 (2007)." href="https://www.nature.com/articles/nm.4030#ref3" >3</a></sup>. 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<sup ><a id="ref-link-abstract-4" title="Pagliuca, F.W. et al. Generation of functional human pancreatic β-cells in vitro. Cell 159, 428–439 (2014)." href="https://www.nature.com/articles/nm.4030#ref4" >4</a></sup>. Strategies to address the immunosuppression concerns include immunoisolation of insulin-producing cells with porous biomaterials that function as an immune barrier<sup ><a id="ref-link-abstract-5" title="Lim, F. & Sun, A.M. Microencapsulated islets as bioartificial endocrine pancreas. Science 210, 908–910 (1980)." href="https://www.nature.com/articles/nm.4030#ref5" >5</a>,<a id="ref-link-abstract-6" title="Soon-Shiong, P. et al. Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Lancet 343, 950–951 (1994)." href="https://www.nature.com/articles/nm.4030#ref6" >6</a></sup>. However, clinical implementation has been challenging because of host immune responses to the implant materials<sup ><a id="ref-link-abstract-7" title="Dolgin, E. Encapsulate this. Nat. Med. 20, 9–11 (2014)." href="https://www.nature.com/articles/nm.4030#ref7" >7</a></sup>. 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 <i >in vivo</i> 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 <i >in vivo</i> glucose responsiveness demonstrated therapeutically relevant glycemic control. Implants retrieved after 174 d contained viable insulin-producing cells.</p>
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