Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived ß cells.
Nat Cell Biol
; 21(2): 263-274, 2019 02.
Article
in En
| MEDLINE
| ID: mdl-30710150
ABSTRACT
Despite advances in the differentiation of insulin-producing cells from human embryonic stem cells, the generation of mature functional ß cells in vitro has remained elusive. To accomplish this goal, we have developed cell culture conditions to closely mimic events occurring during pancreatic islet organogenesis and ß cell maturation. In particular, we have focused on recapitulating endocrine cell clustering by isolating and reaggregating immature ß-like cells to form islet-sized enriched ß-clusters (eBCs). eBCs display physiological properties analogous to primary human ß cells, including robust dynamic insulin secretion, increased calcium signalling in response to secretagogues, and improved mitochondrial energization. Notably, endocrine cell clustering induces metabolic maturation by driving mitochondrial oxidative respiration, a process central to stimulus-secretion coupling in mature ß cells. eBCs display glucose-stimulated insulin secretion as early as three days after transplantation in mice. In summary, replicating aspects of endocrine cell clustering permits the generation of stem-cell-derived ß cells that resemble their endogenous counterparts.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Differentiation
/
Insulin-Secreting Cells
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Embryonic Stem Cells
/
Endocrine Cells
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Fibroblasts
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Human Embryonic Stem Cells
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Cell Biol
Year:
2019
Type:
Article
Affiliation country:
United States