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

Cell Stem Cell. 2021 Aug 31;S1934-5909(21)00338-6. doi: 10.1016/j.stem.2021.08.001. Online ahead of print.

Abstract

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.

Keywords: beta cells; embryonic stem cells; endothelial cells; islet transplantation; microvessels; pancreatic progenitors; regenerative medicine; subcutaneous; type 1 diabetes; vascularization.