Ameliorating Type 1 Diabetes In Mice Via Implantation Of Apa Microencapsulated Human Stem Cell-Derived Islets

Objective: Human pluripotent stem cells derived islets (SC-islets) provide a promising alternative source for beta cell replacement therapies for type 1 diabetes, while facing immune-rejection risks. Recent studies show that alginate-poly-L-lysine-alginate (APA) microcapsules have potentials to overcome the need for immunosuppression in allogeneic transplantation. In this study, APA encapsulated SC-islets were implanted into type 1 diabetes immune-competent mice models, to explore their ability to treat diabetes. Method: First, we optimized differentiation method, SC-islets’ ratio of mature β cells and in vitro glucose response were measured; SC-islets encapsulated with APA were implanted into the intraperitoneal space of C57BL/6 STZ-induced diabetic mice (n=8), and blood glucose levels were further monitored. Result: After optimization, SC-islets mature β cells (NKX6.1+/C-peptide+) reach 43.72 ± 1.62% (previous data was 21.01± 4.07%), and C-peptide positive cells increased from 34.93 ± 10.05% to 60.86 ± 1.15%. The SC-islets also included α or Δ cells, and responded to multiple sequential high-glucose challenges (insulin secreted ranged 2.10-3.27 μIU/103 cells). Then APA encapsulated SC-islets were implanted into the intraperitoneal space of diabetes mice. The fasting blood glucose decreased to normal level (3.70 ± 0.93 mM) on day 1 post-transplant, and the blood glucose maintained normal for 11 days. Similarly, random blood glucose returned to normal levels (11.01 ± 4.63 mM) on day 7 post-transplant. Conclusion: Optimized SC-islets had a higher proportion of mature β cells and improved glucose response functions. The in vivo results showed that SC-islets in APA microcapsules can rapidly ameliorate hyperglycemia in diabetic mouse, while the duration time need further improvement through inhibiting fibrosis in alginate microspheres. Our results indicate that microencapsulated allogeneic SC-islets have potentials to treat diabetes. Disclosure L. Guo: None. Q. Pan: None. Y. Song: None. Y. Cao: None. Z. Ou: None. X. Chen: None. W. Li: None. X. Tang: None.