Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient

Shusen Wang; Yuanyuan Du; Boya Zhang; Gaofan Meng; Zewen Liu; Soon Yi Liew; Rui Liang; Zhengyuan Zhang; Xiangheng Cai; Shuangshuang Wu; Wei Gao; Dewei Zhuang; Jiaqi Zou; Hui Huang; Mingyang Wang; Xiaofeng Wang; Xuelian Wang; Ting Liang; Tengli Liu; Jiabin Gu; Na Liu; Yanling Wei; Xuejie Ding; Yue Pu; Yixiang Zhan; Yu Luo; Peng Sun; Shuangshuang Xie; Jiuxia Yang; Yiqi Weng; Chunlei Zhou; Zhenglu Wang; Shuang Wang; Hongkui Deng; Zhongyang Shen

doi:10.1016/j.cell.2024.09.004

Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient

Cell. 2024 Oct 31;187(22):6152-6164.e18. doi: 10.1016/j.cell.2024.09.004. Epub 2024 Sep 25.

Authors

Shusen Wang¹, Yuanyuan Du², Boya Zhang³, Gaofan Meng², Zewen Liu³, Soon Yi Liew², Rui Liang³, Zhengyuan Zhang⁴, Xiangheng Cai³, Shuangshuang Wu⁵, Wei Gao³, Dewei Zhuang⁵, Jiaqi Zou³, Hui Huang⁵, Mingyang Wang⁶, Xiaofeng Wang⁵, Xuelian Wang³, Ting Liang⁵, Tengli Liu³, Jiabin Gu⁵, Na Liu³, Yanling Wei⁵, Xuejie Ding³, Yue Pu⁵, Yixiang Zhan³, Yu Luo⁵, Peng Sun³, Shuangshuang Xie⁷, Jiuxia Yang³, Yiqi Weng⁸, Chunlei Zhou⁹, Zhenglu Wang³, Shuang Wang¹⁰, Hongkui Deng¹¹, Zhongyang Shen¹²

Affiliations

¹ Research Institute of Transplant Medicine, Organ Transplant Center, Tianjin First Central Hospital, School of Medicine, Nankai University, NHC Key Laboratory for Critical Care Medicine, Key Laboratory of Transplant Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China. Electronic address: [email protected].
² School of Basic Medical Sciences, MOE Engineering Research Center of Regenerative Medicine, 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 100191, China; Hangzhou Reprogenix Bioscience, Hangzhou, China.
³ Research Institute of Transplant Medicine, Organ Transplant Center, Tianjin First Central Hospital, School of Medicine, Nankai University, NHC Key Laboratory for Critical Care Medicine, Key Laboratory of Transplant Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China.
⁴ School of Basic Medical Sciences, MOE Engineering Research Center of Regenerative Medicine, 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 100191, China.
⁵ Hangzhou Reprogenix Bioscience, Hangzhou, China.
⁶ Department of Ultrasound, Tianjin First Central Hospital, Nankai University, Tianjin 300192, China.
⁷ Radiology Department, Tianjin First Central Hospital, Nankai University, Tianjin 300192, China.
⁸ Department of Anesthesiology, Tianjin First Central Hospital, Nankai University, Tianjin 300192, China.
⁹ Department of Medical Laboratory, Tianjin First Central Hospital, Nankai University, Tianjin 300192, China.
¹⁰ Department of Plastic and Burn, Tianjin First Central Hospital, Nankai University, Tianjin 300192, China.
¹¹ School of Basic Medical Sciences, MOE Engineering Research Center of Regenerative Medicine, 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 100191, China; China Changping Laboratory, Beijing 102206, China. Electronic address: [email protected].
¹² Research Institute of Transplant Medicine, Organ Transplant Center, Tianjin First Central Hospital, School of Medicine, Nankai University, NHC Key Laboratory for Critical Care Medicine, Key Laboratory of Transplant Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China. Electronic address: [email protected].

PMID: 39326417
DOI: 10.1016/j.cell.2024.09.004

Abstract

We report the 1-year results from one patient as the preliminary analysis of a first-in-human phase I clinical trial (ChiCTR2300072200) assessing the feasibility of autologous transplantation of chemically induced pluripotent stem-cell-derived islets (CiPSC islets) beneath the abdominal anterior rectus sheath for type 1 diabetes treatment. The patient achieved sustained insulin independence starting 75 days post-transplantation. The patient's time-in-target glycemic range increased from a baseline value of 43.18% to 96.21% by month 4 post-transplantation, accompanied by a decrease in glycated hemoglobin, an indicator of long-term systemic glucose levels at a non-diabetic level. Thereafter, the patient presented a state of stable glycemic control, with time-in-target glycemic range at >98% and glycated hemoglobin at around 5%. At 1 year, the clinical data met all study endpoints with no indication of transplant-related abnormalities. Promising results from this patient suggest that further clinical studies assessing CiPSC-islet transplantation in type 1 diabetes are warranted.

Keywords: abdominal anterior rectus sheath; cell therapy; chemical reprogramming; chemically induced pluripotent stem cells; diabetes; insulin independence; islet transplantation; personalized medicine; regenerative medicine; stem-cell-derived islets.

Publication types

Clinical Trial, Phase I
Case Reports

MeSH terms

Adult
Blood Glucose / metabolism
Diabetes Mellitus, Type 1* / therapy
Glycated Hemoglobin / metabolism
Humans
Induced Pluripotent Stem Cells* / cytology
Induced Pluripotent Stem Cells* / metabolism
Insulin / metabolism
Islets of Langerhans / metabolism
Islets of Langerhans Transplantation* / methods
Male
Rectus Abdominis / metabolism

Substances

Glycated Hemoglobin
Blood Glucose
Insulin