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Updated: Jan 8, 2026
Scaffold-supported Transplantation of Islets in the Epididymal Fat Pad of Diabetic Mice
Published on: July 23, 2017
Pilot Study: Functional Survival of Human Stem Cell-Derived Islets Microencapsulated With Alginate Incorporating
Kento Kawai1, Fatma Dogan1, David A Alagpulinsa1
1Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Glucose-responsive insulin-secreting stem cell-derived islet-like cells (SC-islets) are a promising source for beta cell replacement to treat type 1 diabetes (T1D). However, immune rejection and limited function of SC-islets post-transplantation are key barriers to this treatment. We previously reported glycemic control and prolonged function of SC-islets microencapsulated in alginate that incorporates the pro-survival and immunomodulatory chemokine CXCL12 in immunocompetent diabetic mice without systemic immune suppression. Here, in a pilot study, we translated this SC-islet microencapsulation approach in nonhuman primates (NHPs) via transplantation of a therapeutic dose of SC-islets microencapsulated in alginate incorporating CXCL12 into the greater omental sac of a healthy and a diabetic NHP. We demonstrate that treatment did not cause metabolic dysfunction over a 6-month period in the NHPs. The healthy NHP maintained stable C-peptide and blood glucose levels, while the diabetic NHP had detectable serum C-peptide through 13 weeks post-transplant and a significant reduction in exogenous insulin requirements compared with a corresponding diabetic NHP recipient in the absence of immunosuppressive treatment. Serum biochemistry as well as hematological and immunological parameters of the NHPs remained normal throughout the post-transplantation period. At termination, the retrieved microencapsulated SC-islets were predominantly free floating without pericapsular fibrotic overgrowth and were glucose-responsive, expressing all major endocrine cell markers, albeit a significant decrease in viability compared with pre-transplant levels. Overall, these findings demonstrate feasibility, safety, and function of microencapsulated SC-islets in two NHPs in this small pilot study and our dataset supports further investigation of this approach toward clinical translation.
Glucose-responsive insulin-secreting stem cell-derived islet-like cells (SC-islets) are a promising source for beta cell replacement to treat type 1 diabetes (T1D). However, immune rejection and limited function of SC-islets post-transplantation are key barriers to this treatment. We previously reported glycemic control and prolonged function of SC-islets microencapsulated in alginate that incorporates the pro-survival and immunomodulatory chemokine CXCL12 in immunocompetent diabetic mice without systemic immune suppression. Here, in a pilot study, we translated this SC-islet microencapsulation approach in nonhuman primates (NHPs) via transplantation of a therapeutic dose of SC-islets microencapsulated in alginate incorporating CXCL12 into the greater omental sac of a healthy and a diabetic NHP. We demonstrate that treatment did not cause metabolic dysfunction over a 6-month period in the NHPs. The healthy NHP maintained stable C-peptide and blood glucose levels, while the diabetic NHP had detectable serum C-peptide through 13 weeks post-transplant and a significant reduction in exogenous insulin requirements compared with a corresponding diabetic NHP recipient in the absence of immunosuppressive treatment. Serum biochemistry as well as hematological and immunological parameters of the NHPs remained normal throughout the post-transplantation period. At termination, the retrieved microencapsulated SC-islets were predominantly free floating without pericapsular fibrotic overgrowth and were glucose-responsive, expressing all major endocrine cell markers, albeit a significant decrease in viability compared with pre-transplant levels. Overall, these findings demonstrate feasibility, safety, and function of microencapsulated SC-islets in two NHPs in this small pilot study and our dataset supports further investigation of this approach toward clinical translation.
