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

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收录情况： ◇ 自然指数

作者：
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 [3] ; Xiaozhong Peng [4,9] ; Hongkui Deng [1] ;
机构： [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-TsinghuaCenter for Life Sciences, Peking University, Beijing, China [2]Hangzhou Reprogenix Bioscience, Hangzhou, China [3]Organ Transplant Center, NHC KeyLaboratory for Critical Care Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, China [4]Institute of Medical Biology, Chinese Academyof 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]State Key Laboratory of Medical Molecular Biology,Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, ChineseAcademy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
出处：
DOI： 10.1038/s41591-021-01645-7
ISSN：

摘要：
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.© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

基金：
This work was supported by the National Key Research and Development Program of China (2017YFA0103000 to H.D., 2018YFA0108102 to H.D. and 2020YFA0803704 to S.W.); the National Natural Science Foundation of China (31521004 to H.D., 31730059 to H.D., 82070805 to S.W., 81870535 to S.W., 82100840 to T.L. and 82100841 to R.L.); the Key Project and Team Program of Tianjin (XB202011 to S.W.); and the CAMS Innovation Fund for Medical Sciences (2021-1-I2M-024 to X.P.).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验 1 区 生化与分子生物学 1 区 细胞生物学
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 生化与分子生物学 1 区 细胞生物学 1 区 医学：研究与实验
第一作者：
第一作者机构： [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-TsinghuaCenter for Life Sciences, Peking University, Beijing, China [2]Hangzhou Reprogenix Bioscience, Hangzhou, China
共同第一作者：
通讯作者：
通讯机构： [4]Institute of Medical Biology, Chinese Academyof Medical Sciences and Peking Union Medical College, Yunnan, China [9]State Key Laboratory of Medical Molecular Biology,Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, ChineseAcademy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China
推荐引用方式(GB/T 7714)：
Yuanyuan Du,Zhen Liang,Shusen Wang,et al.Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates[J].Nature medicine.2022,28(2):272-282.doi:10.1038/s41591-021-01645-7.
APA：
Yuanyuan Du,Zhen Liang,Shusen Wang,Dong Sun,Xiaofeng Wang...&Hongkui Deng.(2022).Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates.Nature medicine,28,(2)
MLA：
Yuanyuan Du,et al."Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates".Nature medicine 28..2(2022):272-282

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