Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo
Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo
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DOI：
10.1038/nbt1393
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发表时间：
2008-04-01
影响因子：
46.9
通讯作者：
Baetge, Emmanuel E.
中科院分区：
文献类型：
--
作者：
Kroon, Evert;Martinson, Laura A.;Baetge, Emmanuel E.
可再生的人类β细胞供应将极大地有助于糖尿病细胞疗法的开发。在此我们表明，源自人类胚胎干细胞（hES）的胰腺内胚层在植入小鼠体内后能高效地产生对葡萄糖有反应的内分泌细胞。在对植入小鼠进行葡萄糖刺激时，在血清中检测到的人类胰岛素和C肽水平与移植了约3000个人类胰岛的小鼠相似。此外，植入后产生的表达胰岛素的细胞展现出功能性β细胞的许多特性，包括关键的β细胞转录因子的表达、胰岛素原的正确加工以及成熟内分泌分泌颗粒的存在。最后，在一项治疗潜力测试中，我们证明植入源自hES细胞的胰腺内胚层可预防链脲佐菌素诱导的高血糖。总之，这些数据提供了确凿的证据，表明hES细胞能够产生对葡萄糖有反应的、分泌胰岛素的细胞。
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.