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Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived β cells.

Abstract：

:Despite advances in the differentiation of insulin-producing cells from human embryonic stem cells, the generation of mature functional β 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 β cell maturation. In particular, we have focused on recapitulating endocrine cell clustering by isolating and reaggregating immature β-like cells to form islet-sized enriched β-clusters (eBCs). eBCs display physiological properties analogous to primary human β 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 β 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 β cells that resemble their endogenous counterparts.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Nair GG,Liu JS,Russ HA,Tran S,Saxton MS,Chen R,Juang C,Li ML,Nguyen VQ,Giacometti S,Puri S,Xing Y,Wang Y,Szot GL,Oberholzer J,Bhushan A,Hebrok M

doi

10.1038/s41556-018-0271-4

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

263-274

issue

2

eissn

1465-7392

issn

1476-4679

pii

10.1038/s41556-018-0271-4

journal_volume

21

pub_type

杂志文章

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