Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates
Abstract
Human pluripotent stem-cell-derived islets (hPSC-islets) are a promising cell resource for diabetes treatment 1,2 . However, this therapeutic strategy has not been systematically assessed in large animal models physiologically similar to humans, such as non-human primates 3 . 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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SC-islets were used to help treat diabetic non-human primates.
“Recently, these SC-islets were also used to help treat diabetic non-human primates.45,46”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [45]
While the primates did not achieve complete insulin independence, the transplanted SC-islets significantly reduced their insulin requirements and greatly improved their glycemic control.
“While the primates did not achieve complete insulin independence, the transplanted SC-islets significantly reduced their insulin requirements and greatly improved their glycemic control, further illustrating their potential utility as a therapy.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [45]
A similar dispersion freezing method has been successfully used in SC-islet transplantation into non-human primates.
“A similar dispersion freezing method has been successfully used in the context of SC-islet transplantation into non-human primates.45,46”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [45]
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Wang, S., Du, Y., Zhang, B., Meng, G., Liu, Z., Liew, S. Y., Liang, R., Zhang, Z., Cai, X., Wu, S., et al. (2024) · Cell · doi:10.1016/j.cell.2024.09.004 · Cited by 281 · see citing works
Self-citationDevelopments in stem cell-derived islet replacement therapy for treating type 1 diabetes
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Highly efficient and rapid generation of human pluripotent stem cells by chemical reprogramming.
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- Authors
- Du, Y., Liang, Z., Wang, S., Sun, D., Wang, X., Liew, S. Y., Lu, S., Wu, S., Jiang, Y., Wang, Y., Zhang, B., Yu, W., Lu, Z., Pu, Y., Zhang, Y., Long, H., Xiao, S., Liang, R., Zhang, Z., Guan, J., Wang, J., Ren, H., Wei, Y., Zhao, J., Sun, S., Liu, T., Meng, G., Wang, L., Gu, J., Wang, T., Liu, Y., Li, C., Tang, C., Shen, Z., Peng, X., & Deng, H.
- Affiliations
- Peking University (CN)
- Nankai University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Shen, Zhongyang
- Peng, Xiaozhong
- Deng, Hongkui
- ORCID
- 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
- Pu, Yue
- Zhang, Yun
- Xiao, Shanshan
- Liang, Rui
- Zhang, Zhengyuan
- Guan, Jingyang
- Wang, Jinlin
- Ren, Huixia
- Wei, Yanling
- Sun, Shicheng
- Meng, Gaofan
- Wang, Le
- Gu, Jiabin
- Wang, Tao
- Liu, Yinan
- Li, Cheng
- Tang, Chao
- Shen, Zhongyang
- Peng, Xiaozhong
- Deng, Hongkui
- Venue
- Nature Medicine
- Published
- 2022-02
- Volume
- 28
- Issue
- 2
- Pages
- 272-282
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W4210666526
- Cited by
- 155
- References
- 10
- Citations by year
- 2026: 26 · 2025: 39 · 2024: 43 · 2023: 30 · 2022: 17
- FWCI
- 30.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- diabetes treatment, islet transplantation, non-human primates, macaque, glycemic control, insulin secretion, C-peptide, HbA1c, preclinical translation
- MeSH terms
- Animals, Blood Glucose, Diabetes Mellitus, Experimental, Humans, Insulin, Islets of Langerhans, Primates, Islets of Langerhans Transplantation
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