Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo.

Abstract:

:Development of a cell therapy for diabetes would be greatly aided by a renewable supply of human beta-cells. Here we show that pancreatic endoderm derived from human embryonic stem (hES) cells efficiently generates glucose-responsive endocrine cells after implantation into mice. Upon glucose stimulation of the implanted mice, human insulin and C-peptide are detected in sera at levels similar to those of mice transplanted with approximately 3,000 human islets. Moreover, the insulin-expressing cells generated after engraftment exhibit many properties of functional beta-cells, including expression of critical beta-cell transcription factors, appropriate processing of proinsulin and the presence of mature endocrine secretory granules. Finally, in a test of therapeutic potential, we demonstrate that implantation of hES cell-derived pancreatic endoderm protects against streptozotocin-induced hyperglycemia. Together, these data provide definitive evidence that hES cells are competent to generate glucose-responsive, insulin-secreting cells.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Kroon E,Martinson LA,Kadoya K,Bang AG,Kelly OG,Eliazer S,Young H,Richardson M,Smart NG,Cunningham J,Agulnick AD,D'Amour KA,Carpenter MK,Baetge EE

doi

10.1038/nbt1393

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

443-52

issue

4

eissn

1087-0156

issn

1546-1696

pii

nbt1393

journal_volume

26

pub_type

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