Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates Journal Articles uri icon

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abstract

  • Human pluripotent stem-cell-derived islets (hPSC-islets) are a promising cell resource for diabetes treatment1,2. However, this therapeutic strategy has not been systematically assessed in large animal models physiologically similar to humans, such as non-human primates3. 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.

authors

  • 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

publication date

  • February 2022