Du Yuanyuan, Liang Zhen, Wang Shusen, Sun Dong, Wang Xiaofeng, Liew Soon Yi, Lu Shuaiyao, Wu Shuangshuang, Jiang Yong, Wang Yaqi, Zhang Boya, Yu Wenhai, Lu Zhi, Pu Yue, Zhang Yun, Long Haiting, Xiao Shanshan, Liang Rui, Zhang Zhengyuan, Guan Jingyang, Wang Jinlin, Ren Huixia, Wei Yanling, Zhao Jiaxu, Sun Shicheng, Liu Tengli, Meng Gaofan, Wang Le, Gu Jiabin, Wang Tao, Liu Yinan, Li Cheng, Tang Chao, Shen Zhongyang, Peng Xiaozhong, Deng Hongkui
MOE Engineering Research Center of Regenerative Medicine, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
Hangzhou Reprogenix Bioscience, Hangzhou, China.
Nat Med. 2022 Feb;28(2):272-282. doi: 10.1038/s41591-021-01645-7. Epub 2022 Feb 3.
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.
人多能干细胞衍生的胰岛（hPSC - 胰岛）是糖尿病治疗中一种很有前景的细胞资源。然而，这种治疗策略尚未在生理上与人类相似的大型动物模型（如非人灵长类动物）中进行系统评估。在本研究中，我们从人化学诱导多能干细胞中生成了胰岛（hCiPSC - 胰岛），并表明将一剂hCiPSC - 胰岛经门静脉输注到糖尿病非人灵长类动物体内可有效恢复内源性胰岛素分泌并改善血糖控制。所有接受者的空腹和餐前平均血糖水平显著降低，同时伴有餐后或葡萄糖反应性C肽释放以及体重总体增加。值得注意的是，在四只长期随访的猕猴中，与峰值相比，平均糖化血红蛋白下降超过2%，而移植后15周平均外源性胰岛素需求减少了49%。总体而言，我们的研究结果表明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 - 胰岛临床转化向前迈出了重要一步。
