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 Biotechnoljournal_title
Nature biotechnologyauthors
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 EEdoi
10.1038/nbt1393subject
Has Abstractpub_date
2008-04-01 00:00:00pages
443-52issue
4eissn
1087-0156issn
1546-1696pii
nbt1393journal_volume
26pub_type
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