Microvessels support engraftment and functionality of human islets and hESC-derived pancreatic progenitors in diabetes models

Islet transplantation is a promising treatment for type 1 diabetes (T1D), yet the low donor pool, poor islet engraftment, and life-long immunosuppression prevent it from becoming the standard of care. Human embryonic stem cell (hESC)-derived pancreatic cells could eliminate donor shortages, but interventions to improve graft survival are needed. Here, we enhanced subcutaneous engraftment by employing a unique vascularization strategy based on ready-made microvessels (MVs) isolated from the adipose tissue. This resulted in improved cell survival and effective glucose response of both human islets and hESC-derived pancreatic cells, which ameliorated preexisting diabetes in three mouse models of T1D. [Display omitted] •Microvessels support engraftment of pancreatic cells in the subcutaneous site•Transplantation of microvessels with pancreatic cells accelerates diabetes reversal•Microvessels enable diabetes reversal with a subtherapeutic dose of human islets•Microvessels replenish the intraislet vasculature of the transplanted human islets Aghazadeh et al. show that transplantation of adipose-derived microvessels in the subcutaneous space supports early connection to the host vasculature, promoting engraftment and function of either hESC-derived pancreatic progenitors or human islets. This strategy resulted in improved graft survival and effective glucose response, leading to accelerated reversal of diabetes.