Advances in Cell Replacement Therapies for Diabetes

作者：Bernhard J. Hering, Michael R. Rickels, Melena D. Bellin, Jeffrey R. Millman, Alice A. Tomei, Andrés J. Garcı́a, Haval Shirwan, Cherie L. Stabler, Minglin Ma, Yi Peng, Xunrong Luo, Qizhi Tang, Sabarinathan Ramachandran, José Oberholzer, Camillo Ricordi, Timothy J. Kieffer, A. M. James Shapiro · 发表于：Diabetes · 年份：2025 · 被引用次数：37 · 研究领域：Pancreatic function and diabetes、Diabetes and associated disorders、Diabetes Management and Research

Islet cell replacement therapies have evolved as a viable treatment option for type 1 diabetes complicated by problematic hypoglycemia and glycemic lability. Refinements of islet manufacturing, islet transplantation procedures, peritransplant recipient management, and immunosuppressive protocols allowed most recipients to achieve favorable outcomes. Subsequent phase 3 trials of transplantation of deceased donor islets documented the effectiveness of transplanted islets in restoring near-normoglycemia, glycemic stability, and protection from severe hypoglycemia, with an acceptable safety profile for the enrolled high-risk population. Health authorities in several countries have approved deceased donor islet transplantation for treating patients with type 1 diabetes and recurrent severe hypoglycemia. These achievements amplified academic and industry efforts to generate pluripotent stem cell-derived β-cells through directed differentiation for β-cell replacement. Preliminary results of ongoing clinical trials suggest that the transplantation of stem cell-derived β-cells can consistently restore insulin independence in immunosuppressed recipients with type 1 diabetes, thus signaling the profound progress made in generating an unlimited and a uniform supply of cells for transplant. Avoiding the risks of chronic immunosuppression represents the next frontier. Several strategies have entered or are approaching clinical investigation, including immune-isolating islets, engineering i...