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

E Kroon, LA Martinson, K Kadoya, AG Bang… - Nature …, 2008 - nature.com
E Kroon, LA Martinson, K Kadoya, AG Bang, OG Kelly, S Eliazer, H Young, M Richardson
Nature biotechnology, 2008nature.com
Abstract Development of a cell therapy for diabetes would be greatly aided by a renewable
supply of human β-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 …
Abstract
Development of a cell therapy for diabetes would be greatly aided by a renewable supply of human β-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 β-cells, including expression of critical β-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.
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