Abstract

Development of a cell therapy for diabetes would be greatly aided by a renewable supply of human -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 3,000 human islets. Moreover, the insulin-expressing cells generated after engraftment exhibit many properties of functional -cells, including expression of critical -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.

1. Novocell, Inc., 3550 General Atomics Ct., San Diego, California 92121, USA.

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