2026-04-19T13:19:13Zhttps://recercat.cat/oai/request

oai:recercat.cat:10230/528422025-12-12T02:29:39Zcom_2072_6col_2072_452952

00925njm 22002777a 4500 dc Balboa, Diego author 2022-04-07T06:10:33Z 2022-04-07T06:10:33Z 2022 Data de publicació electrònica: 03-03-2022 Transplantation of pancreatic islet cells derived from human pluripotent stem cells is a promising treatment for diabetes. Despite progress in the generation of stem-cell-derived islets (SC-islets), no detailed characterization of their functional properties has been conducted. Here, we generated functionally mature SC-islets using an optimized protocol and benchmarked them comprehensively against primary adult islets. Biphasic glucose-stimulated insulin secretion developed during in vitro maturation, associated with cytoarchitectural reorganization and the increasing presence of alpha cells. Electrophysiology, signaling and exocytosis of SC-islets were similar to those of adult islets. Glucose-responsive insulin secretion was achieved despite differences in glycolytic and mitochondrial glucose metabolism. Single-cell transcriptomics of SC-islets in vitro and throughout 6 months of engraftment in mice revealed a continuous maturation trajectory culminating in a transcriptional landscape closely resembling that of primary islets. Our thorough evaluation of SC-islet maturation highlights their advanced degree of functionality and supports their use in further efforts to understand and combat diabetes. We are grateful to the Nordic Network for Islet Transplantation (supported by the strategic grant consortium Excellence of Diabetes Research in Sweden, EXODIAB. This study was supported by the Academy of Finland grant 297466 and MetaStem Center of Excellence grant 312437 (to T.O., V.H., P.K.), the Sigrid Jusélius Foundation Grant (to T.O.) and the Helsinki University Hospital Research Funds (to T.O.) and an EMBO Long-Term Fellowship ALT295-2019 (to D.B.). Additional funding was provided by the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 115797 (INNODIA) and 945268 (INNODIA HARVEST). This Joint Undertaking receives support from the Union’s Horizon 2020 research and innovation program and the European Federation of Pharmaceutical Industries and Associations Diabetis -- Tractament Pàncrees -- Malalties Genètica Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells