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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
Nature medicine, 02/2022, Volume: 28, Issue: 2Journal Article
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.
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