TY - JOUR
T1 - Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells
AU - Balboa, Diego
AU - Barsby, Tom
AU - Lithovius, Vaino
AU - Saarimaki-Vire, Jonna
AU - Omar-Hmeadi, Muhmmad
AU - Dyachok, Oleg
AU - Montaser, Hossam
AU - Lund, Per-Eric
AU - Yang, Mingyu
AU - Ibrahim, Hazem
AU - Naatanen, Anna
AU - Chandra, Vikash
AU - Vihinen, Helena
AU - Jokitalo, Eija
AU - Kvist, Jouni
AU - Ustinov, Jarkko
AU - Nieminen, Anni I.
AU - Kuuluvainen, Emilia
AU - Hietakangas, Ville
AU - Katajisto, Pekka
AU - Lau, Joey
AU - Carlsson, Per-Ola
AU - Barg, Sebastian
AU - Tengholm, Anders
AU - Otonkoski, Timo
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
UR - https://res.slu.se/id/publ/131977
U2 - 10.1038/s41587-022-01219-z
DO - 10.1038/s41587-022-01219-z
M3 - Journal article
C2 - 35241836
SN - 1087-0156
VL - 40
SP - 1042
EP - 1055
JO - Nature Biotechnology
JF - Nature Biotechnology
IS - 7
ER -