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

被引：1331

作者：

Kroon, Evert ^{[1
]}

Martinson, Laura A. ^{[1
]}

Kadoya, Kuniko ^{[1
]}

Bang, Anne G. ^{[1
]}

Kelly, Olivia G. ^{[1
]}

Eliazer, Susan ^{[1
]}

Young, Holly ^{[1
]}

Richardson, Mike ^{[1
]}

Smart, Nora G. ^{[1
]}

Cunningham, Justine ^{[1
]}

Agulnick, Alan D. ^{[1
]}

D'Amour, Kevin A. ^{[1
]}

Carpenter, Melissa K. ^{[1
]}

Baetge, Emmanuel E. ^{[1
]}

机构：

[1] Novocell Inc, San Diego, CA 92121 USA

来源：

NATURE BIOTECHNOLOGY | 2008年 / 26卷 / 04期

关键词：

D O I：

10.1038/nbt1393

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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 similar to 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.

引用

收藏

页码：443 / 452

页数：10

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