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

• Published in: Cell stem cell Vol. 28; no. 11; pp. 1936 - 1949.e8
• Main Authors: Aghazadeh, Yasaman, Poon, Frankie, Sarangi, Farida, Wong, Frances T.M., Khan, Safwat T., Sun, Xuetao, Hatkar, Rupal, Cox, Brian J., Nunes, Sara S., Nostro, M. Cristina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.11.2021
• Subjects: Animals; beta cells; Diabetes Mellitus, Type 1 - therapy; embryonic stem cells; endothelial cells; Human Embryonic Stem Cells; Humans; islet transplantation; Islets of Langerhans; Islets of Langerhans Transplantation; Mice; Microvessels; pancreatic progenitors; regenerative medicine; subcutaneous; type 1 diabetes; vascularization; subcutaneous; pancreatic progenitors; endothelial cells; type 1 diabetes; embryonic stem cells; regenerative medicine; islet transplantation; vascularization; beta cells; microvessels
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2021.08.001

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.