Pilot Study: Functional Survival of Human Stem Cell-Derived Islets Microencapsulated With Alginate Incorporating...

Area of Science:

• Regenerative Medicine
• Endocrinology
• Immunology

Background:

• Type 1 diabetes (T1D) treatment faces challenges with beta cell replacement due to immune rejection and limited function of stem cell-derived islet-like cells (SC-islets).
• Previous studies showed SC-islets encapsulated in alginate with CXCL12 improved glycemic control in diabetic mice without immunosuppression.

Purpose of the Study:

• To assess the feasibility and safety of microencapsulated SC-islets incorporating CXCL12 in nonhuman primates (NHPs).
• To evaluate the metabolic impact and function of SC-islets post-transplantation in healthy and diabetic NHPs.

Main Methods:

• Transplantation of SC-islets microencapsulated in alginate with CXCL12 into the greater omental sac of two NHPs (one healthy, one diabetic).
• Monitoring of metabolic parameters, serum C-peptide, insulin requirements, and immunological markers for 6 months.
• Assessment of retrieved microencapsulated SC-islets for viability, fibrotic overgrowth, and glucose responsiveness.

Main Results:

• No metabolic dysfunction was observed in either NHP over the 6-month study period.
• The diabetic NHP showed detectable C-peptide for 13 weeks and reduced insulin needs, without immunosuppression.
• NHPs maintained normal serum biochemistry, hematology, and immunology; retrieved SC-islets were glucose-responsive but showed reduced viability.

Conclusions:

• Microencapsulation of SC-islets with CXCL12 is feasible and safe in NHPs.
• This approach shows potential for T1D treatment, warranting further investigation toward clinical translation.
• Further research is needed to optimize SC-islet viability post-transplantation.