Human pancreatic beta-like cells converted from fibroblasts.
Human pancreatic beta-like cells converted from fibroblasts.
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DOI：
10.1038/ncomms10080
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发表时间：
2016-01-06
影响因子：
16.6
通讯作者：
Ding S
中科院分区：
文献类型：
--
作者：
Zhu S;Russ HA;Wang X;Zhang M;Ma T;Xu T;Tang S;Hebrok M;Ding S
胰腺β细胞对于生物医学研究和再生医学具有极大的兴趣。在这里，我们展示了通过采用非整合的附加型重编程因子与特定的生长因子和化合物相结合，人成纤维细胞向内胚层细胞命运的转化。在初始培养时，转化的定形内胚层祖细胞（cDE细胞）被指定为后肠样祖细胞（cPF细胞）。cPF细胞及其衍生物，胰腺内胚层祖细胞（cPE细胞），可以大大扩展。一种筛选方法鉴定了在体外促进cPE细胞分化和成熟为功能性胰腺β样细胞（cPB细胞）的化合物。移植的cPB细胞在体内表现出葡萄糖刺激的胰岛素分泌，并保护小鼠免受化学诱导的糖尿病。总之，我们的研究对未来旨在产生大量功能性β细胞的策略具有重要意义，这可能有助于恢复糖尿病患者的正常血糖。体外产生的胰岛素分泌胰腺β细胞可能会导致新的抗糖尿病疗法。在这里，Zhu等人将人成纤维细胞转化为内胚层祖细胞，这些内胚层祖细胞在体外分化为葡萄糖反应性β样细胞，这些细胞在小鼠中移植后可以防止糖尿病。
Pancreatic beta cells are of great interest for biomedical research and regenerative medicine. Here we show the conversion of human fibroblasts towards an endodermal cell fate by employing non-integrative episomal reprogramming factors in combination with specific growth factors and chemical compounds. On initial culture, converted definitive endodermal progenitor cells (cDE cells) are specified into posterior foregut-like progenitor cells (cPF cells). The cPF cells and their derivatives, pancreatic endodermal progenitor cells (cPE cells), can be greatly expanded. A screening approach identified chemical compounds that promote the differentiation and maturation of cPE cells into functional pancreatic beta-like cells (cPB cells) in vitro. Transplanted cPB cells exhibit glucose-stimulated insulin secretion in vivo and protect mice from chemically induced diabetes. In summary, our study has important implications for future strategies aimed at generating high numbers of functional beta cells, which may help restoring normoglycemia in patients suffering from diabetes. Insulin-producing pancreatic beta cells, generated in vitro, could lead to new anti-diabetic therapies. Here, Zhu et al. convert human fibroblasts into endodermal progenitors that differentiate in vitro into glucose-responsive beta-like cells that, following transplantation in mice, protect from diabetes.