학술논문
Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells.
Document Type
Author
Balboa, Diego; Barsby, Tom; Lithovius, Väinö; Saarimäki-Vire, Jonna; Omar-Hmeadi, Muhmmad; Dyachok, Oleg, 1965; Montaser, Hossam; Lund, Per-Eric; Yang, Mingyu; Ibrahim, Hazem; Näätänen, Anna; Chandra, Vikash; Vihinen, Helena; Jokitalo, Eija; Kvist, Jouni; Ustinov, Jarkko; Nieminen, Anni I; Kuuluvainen, Emilia; Hietakangas, Ville; Katajisto, Pekka; Lau, Joey, 1979; Carlsson, Per-Ola; Barg, Sebastian, 1969; Tengholm, Anders, 1971; Otonkoski, Timo
Source
Nature Biotechnology. 40(7):1042-1055
Subject
Language
English
ISSN
1087-0156
1546-1696
1546-1696
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.