{"id":"doi:10.1038/s41587-022-01219-z","kind":"article","title":"Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells","authors":["Balboa D","Barsby T","Lithovius V","Saarimäki-Vire J","Omar-Hmeadi M","Dyachok O","Montaser H","Lund PE","Yang M","Ibrahim H","Näätänen A","Chandra V","Vihinen H","Jokitalo E","Kvist J","Ustinov J","Nieminen AI","Kuuluvainen E","Hietakangas V","Katajisto P","Lau J","Carlsson PO","Barg S","Tengholm A","Otonkoski T"],"author_count":25,"year":2022,"published":"2022-03-03","venue":"Nature biotechnology","cited_by":359,"doi":"10.1038/s41587-022-01219-z","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41587-022-01219-z","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41587-022-01219-z","updated":null,"pmid":"35241836","pmcid":"PMC9287162","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC9287162/pdf","abstract":"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.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells\" by Balboa D, Barsby T, Lithovius V et al., https://doi.org/10.1038/s41587-022-01219-z, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"gene-cell-therapy","name":"Gene & Cell Therapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}