The scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Transplantation of encapsulated stem cell-derived islets (SC islets) might extend the applicability of islet transplantation to a larger cohort of patients. Transplantation of conformal-coated islets into a confined well-vascularized site allows long-term diabetes reversal in fully MHC-mismatched diabetic mice without immunosuppression. Here, we demonstrated that human SC islets reaggregated from cryopreserved cells display glucose-stimulated insulin secretion in vitro. Importantly, we showed that conformally coated SC islets displayed comparable in vitro function with unencapsulated SC islets, with conformal coating permitting physiological insulin secretion. Transplantation of SC islets into the gonadal fat pad of diabetic NOD-scid mice revealed that both unencapsulated and conformal-coated SC islets could reverse diabetes and maintain human-level euglycemia for more than 80 days. Overall, these results provide support for further evaluation of safety and efficacy of conformal-coated SC islets in larger species.

由于供体的稀缺和免疫抑制的需要，胰岛移植仅限于少数不稳定的 1 型糖尿病患者。封装干细胞衍生胰岛（SC 胰岛）的移植可能会将胰岛移植的适用性扩展到更大的患者群体。将保形包被的胰岛移植到血管化良好的受限部位，可以使 MHC 完全不匹配的糖尿病小鼠长期逆转糖尿病，而无需免疫抑制。在这里，我们证明了从冷冻保存的细胞中重新聚集的人类 SC 胰岛在体外表现出葡萄糖刺激的胰岛素分泌。重要的是，我们表明，保形涂层的 SC 胰岛表现出与未封装的 SC 胰岛相当的体外功能，保形涂层允许生理性胰岛素分泌。将 SC 胰岛移植到糖尿病 NOD-scid 小鼠的性腺脂肪垫中显示，未封装和保形包被的 SC 胰岛都可以逆转糖尿病并维持人类水平的正常血糖超过 80 天。总体而言，这些结果为进一步评估保形涂层 SC 胰岛在较大物种中的安全性和有效性提供了支持。