| Title: |
Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells. |
| Authors: |
Balboa, Diego, Barsby, Tom, Lithovius, Väinö, Saarimäki-Vire, Jonna, Omar-Hmeadi, Muhmmad, Dyachok, Oleg, 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 |
| Source: |
Nature Biotechnology; Jul2022, Vol. 40 Issue 7, p1042-1055, 14p |
| 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. Pancreatic islets derived from stem cells are benchmarked against primary cells. [ABSTRACT FROM AUTHOR] |
|
Copyright of Nature Biotechnology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |
