摘要
人的 pluripotent 干细胞代表功能的胰腺的内分泌的系房间的潜在地无限的来源。这里，我们报导一条高度有效的途径导致人的胚胎的茎(ES ) 细胞和导致的 pluripotent 茎(iPS ) 在一个定义化学药品的文化系统区分进成熟生产胰岛素的细胞的细胞。这条途径获得的区分的人的 ES 房间由流动 cytometry 分析作为 assayed 包括了将近 25% 胰岛素积极的房间，它以比得上成年人的小岛的一种方式响应葡萄糖刺激释放了 insulin/C-peptide。大多数这些生产胰岛素的房间共同表示成熟尾房间特定的标记象 NKX6-1 和 PDX1 那样，在 vivo 显示一个类似的基因表示模式到成年小岛尾房间。在这研究，我们也证明 EGF 便于 PDX1 积极的胰腺的祖先的扩大。而且，我们的协议也成功了高效地导致人的 iPS 房间区分进生产胰岛素的房间。因此，这个工作不仅提供一个新模型在 vitro 学习人的胰腺的专门化和成熟的机制，而且提高为糖尿病的处理利用病人特定的 iPS 房间的可能性。
Human pluripotent stem cells represent a potentially unlimited source of functional pancreatic endocrine lineage cells. Here we report a highly efficient approach to induce human embryonic stem （ES） cells and induced pluripo- tent stem （iPS） cells to differentiate into mature insulin-producing cells in a chemical-defined culture system. The differentiated human ES cells obtained by this approach comprised nearly 25% insulin-positive cells as assayed by flow cytometry analysis, which released insulin/C-peptide in response to glucose stimuli in a manner comparable to that of adult human islets. Most of these insulin-producing cells co-expressed mature β cell-specific markers such as NKX6-1 and PDX1, indicating a similar gene expression pattern to adult islet β cells in vivo. In this study, we also demonstrated that EGF facilitates the expansion of PDXl-positive pancreatic progenitors. Moreover, our protocol also succeeded in efficiently inducing human iPS cells to differentiate into insuIin-producing ceils. Therefore, this work not only provides a new model to study the mechanism of human pancreatic specialization and maturation in vitro, but also enhances the possibility of utilizing patient-specific iPS cells for the treatment of diabetes.
