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  3. Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates

Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates

  • Nat Med. 2022 Feb;28(2):272-282. doi: 10.1038/s41591-021-01645-7.
Yuanyuan Du # 1 2,  Zhen Liang # 1 2,  Shusen Wang # 3,  Dong Sun # 1,  Xiaofeng Wang # 2,  Soon Yi Liew # 1,  Shuaiyao Lu # 4,  Shuangshuang Wu 2,  Yong Jiang 2,  Yaqi Wang 5,  Boya Zhang 3,  Wenhai Yu 4,  Zhi Lu 2,  Yue Pu 6,  Yun Zhang 3,  Haiting Long 4,  Shanshan Xiao 6,  Rui Liang 3,  Zhengyuan Zhang 1,  Jingyang Guan 1,  Jinlin Wang 1,  Huixia Ren 7,  Yanling Wei 2,  Jiaxu Zhao 8,  Shicheng Sun 1,  Tengli Liu 3,  Gaofan Meng 1 2,  Le Wang 3,  Jiabin Gu 2,  Tao Wang 6,  Yinan Liu 1,  Cheng Li 5,  Chao Tang 7,  Zhongyang Shen 9,  Xiaozhong Peng 10 11,  Hongkui Deng 12
Affiliations

Affiliations

  • 1 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.
  • 2 Hangzhou Reprogenix Bioscience, Hangzhou, China.
  • 3 Organ Transplant Center, NHC Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, China.
  • 4 Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • 5 School of Life Sciences, Center for Bioinformatics, Peking University, Beijing, China.
  • 6 Hangzhou Repugene Technology, Hangzhou, China.
  • 7 Center for Quantitative Biology, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
  • 8 State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
  • 9 Organ Transplant Center, NHC Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, China. zhongyangshen@vip.sina.com.
  • 10 Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China. pengxiaozhong@pumc.edu.cn.
  • 11 State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China. pengxiaozhong@pumc.edu.cn.
  • 12 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. hongkui_deng@pku.edu.cn.
  • # Contributed equally.
PMID: 35115708 DOI: 10.1038/s41591-021-01645-7
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.

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