人多能干细胞来源胰岛移植改善糖尿病非人灵长类动物血糖控制的临床前研究

Abstract

Human pluripotent stem-cell-derived islets (hPSC-islets) are a promising cell resource for diabetes treatment 1 , 2 . However, this therapeutic strategy has not been systematically assessed in large animal models physiologically similar to humans, such as non-human primates 3 . In this study, we generated islets from human chemically induced pluripotent stem cells (hCiPSC-islets) and show that a one-dose intraportal infusion of hCiPSC-islets into diabetic non-human primates effectively restored endogenous insulin secretion and improved glycemic control. Fasting and average pre-prandial blood glucose levels significantly decreased in all recipients, accompanied by meal or glucose-responsive C-peptide release and overall increase in body weight. Notably, in the four long-term follow-up macaques, average hemoglobin A1c dropped by over 2% compared with peak values, whereas the average exogenous insulin requirement reduced by 49% 15 weeks after transplantation. Collectively, our findings show the feasibility of hPSC-islets for diabetic treatment in a preclinical context, marking a substantial step forward in clinical translation of hPSC-islets.