He DW, Zhang FR, Zhang HX, Xiao SY, Bi XY, Wang YM, Wang RL, Lu YX, Yin H, Li T. Stem cells-derived islet transplantation toward clinical translation: Divergent strategies and convergent objectives. World J Diabetes 2026; 17(7): 119760 [DOI: 10.4239/wjd.119760]
Corresponding Author of This Article
Tuo Li, Professor, Department of Endocrinology, Shanghai Changzheng Hospital, No. 415 Fengyang Road, Shanghai 200433, China. dr.lituo@smmu.edu.cn
Research Domain of This Article
Transplantation
Article-Type of This Article
review-article
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He DW, Zhang FR, Zhang HX, Xiao SY, Bi XY, Wang YM, Wang RL, Lu YX, Yin H, Li T. Stem cells-derived islet transplantation toward clinical translation: Divergent strategies and convergent objectives. World J Diabetes 2026; 17(7): 119760 [DOI: 10.4239/wjd.119760]
Duo-Wen He, Fu-Rong Zhang, Hong-Xi Zhang, Shu-Yan Xiao, Xiao-Yan Bi, Yi-Man Wang, Ru-Lan Wang, Yi-Xian Lu, Hao Yin, Tuo Li
Duo-Wen He, Hao Yin, Organ Transplant Center, Shanghai Changzheng Hospital, Shanghai 200003, China
Fu-Rong Zhang, Hong-Xi Zhang, Shu-Yan Xiao, Xiao-Yan Bi, Yi-Man Wang, Ru-Lan Wang, Yi-Xian Lu, Tuo Li, Department of Endocrinology, Shanghai Changzheng Hospital, Shanghai 200433, China
Co-first authors: Duo-Wen He and Fu-Rong Zhang.
Co-corresponding authors: Hao Yin and Tuo Li.
Author contributions: Li T and Yin H were responsible for conceptualization; He DW and Zhang FR were responsible for writing—original draft preparation; Zhang HX, Xiao SY and Bi XY were responsible for writing—review and editing; Wang YM, Wang RL and Lu YX were responsible for visualization; Yin H and Li T were responsible for supervision; and all authors have read and agreed to the published version of the manuscript.
AI contribution statement: The main text and our response to reviewers were entirely authored by the authors and not generated by any AI tool. Language polishing was performed by a language-editing company. No AI tools were used in this process. AI tools were not used in the study design or interpretation of results. We confirm that no AI-generated content was included in our manuscript, and all content and figures are original or properly licensed.
Supported by National Natural Science Foundation of China, No. 82595903, No. 82470935, and No. 82470838; and National Key Research and Development Program of China (Disruptive Technology Innovation Special Project), No. 2025YFF1501700.
Conflict-of-interest statement: The authors declare no conflict of interest or relevant financial relationships.
Corresponding author: Tuo Li, Professor, Department of Endocrinology, Shanghai Changzheng Hospital, No. 415 Fengyang Road, Shanghai 200433, China. dr.lituo@smmu.edu.cn
Received: February 6, 2026 Revised: March 8, 2026 Accepted: June 3, 2026 Published online: July 15, 2026 Processing time: 153 Days and 18.4 Hours
Abstract
Diabetes mellitus, a chronic metabolic disease with high global prevalence, is in urgent need of breakthrough therapies due to its high risk of complications and limitations of current treatments. Stem cells-derived differentiated islet transplantation represents a promising therapeutic strategy for diabetes mellitus by enabling the regeneration of functional islet cells and the restoration of endogenous insulin secretion. This review provided a comprehensive overview of stem cells-based islet differentiation and transplantation technologies, including the classification and functional roles of different stem cell types. It systematically compared the current research status and strategic differences among leading centers and platforms. In addition, the major translational challenges were critically analyzed, with particular emphasis on immunological barriers, long term graft function, and clinical scalability, alongside insights drawn from the authors’ clinical experience. Furthermore, this review explored future research directions that are expected to drive clinical translation, including the application of gene editing technologies, the optimization of immunomodulatory strategies, and advances in pancreatic islet cryopreservation. Despite rapid progress in the field, a systematic comparison of stem cells-derived islet strategies, particularly with respect to immune compatibility, manufacturability, and individualized therapeutic potential, remains limited. This review addressed this gap by presenting an integrated analysis of current approaches, contextualized by clinical experience, and by proposing future multidisciplinary strategies that combine gene-editing, localized immunomodulation, and improved cryopreservation techniques to advance stem cell-derived islet transplantation toward broader clinical application.
Core Tip: This review systematically compared leading stem cells-derived islet transplantation strategies, including autologous and allogeneic approaches from key research centers. It highlighted the trade-offs among immunogenicity, scalability, and personalization, and proposed future integrative solutions combining gene editing, localized immunomodulation, and cryopreservation advances to overcome current barriers toward a functional cure for diabetes.
