Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates
Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates
复制标题
人类多能干细胞来源的胰岛可改善非人类灵长类动物的糖尿病
DOI：
10.1038/s41591-021-01645-7
复制
发表时间：
2022-02-03
期刊：
影响因子：
82.9
通讯作者：
Deng, Hongkui
中科院分区：
文献类型：
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作者：
Du, Yuanyuan;Liang, Zhen;Deng, Hongkui
人多能干细胞衍生的胰岛（hPSC-胰岛）是用于糖尿病治疗的有前途的细胞资源。然而，这种治疗策略尚未在生理学上类似于人类的大型动物模型（如非人灵长类动物）中进行系统评估。在这项研究中，我们从人化学诱导的多能干细胞（hCiPSC-胰岛）产生胰岛，并显示将hCiPSC-胰岛单剂量门静脉内输注到糖尿病非人灵长类动物中有效地恢复了内源性胰岛素分泌并改善了血糖控制。所有受试者的空腹和平均餐前血糖水平均显著降低，伴有进餐或葡萄糖反应性C肽释放和体重总体增加。值得注意的是，在四只长期随访的猕猴中，平均血红蛋白A1c与峰值相比下降了2%以上，而平均外源性胰岛素需求在移植后15周减少了49%。总的来说，我们的研究结果显示了hPSC-胰岛在临床前背景下用于糖尿病治疗的可行性，标志着hPSC-胰岛的临床转化向前迈出了实质性的一步。
Human pluripotent stem-cell-derived islets (hPSC-islets) are a promising cell resource for diabetes treatment,. However, this therapeutic strategy has not been systematically assessed in large animal models physiologically similar to humans, such as non-human primates. 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.