Human bone marrow mesenchymal stem cells differentiate into insulin-producing cells upon microenvironmental manipulation in vitro
Human bone marrow mesenchymal stem cells differentiate into insulin-producing cells upon microenvironmental manipulation in vitro
复制标题
人骨髓间充质干细胞通过体外微环境操作分化为胰岛素产生细胞
DOI：
10.1016/j.diff.2009.01.001
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发表时间：
2009-06-01
期刊：
影响因子：
2.9
通讯作者：
Wu, Yu-Lian
中科院分区：
文献类型：
--
作者：
Xie, Qiu-Ping;Huang, Hai;Wu, Yu-Lian
近年来研究发现，啮齿类动物骨髓中的多能间充质干细胞（MSCs）在体外具有生成胰岛素分泌细胞（IPC）的能力。然而，对人类BM-MSC的这种能力知之甚少。我们开发了一种非遗传方法来诱导人BM-MSCs转分化为表型和功能上的IPC。将来自12个人供体的BM-MSC在特定条件下顺序培养。系统评价其向β细胞表型的分化程度。具体而言，诱导后，人BM-MSCs形成含有IPC的球状胰岛样簇，这通过双硫腙（DTZ）染色和电子显微镜进一步证实。这些IPC表达与胰腺β细胞的发育或功能相关的多种基因（包括NKX6.1、ISL-1、Beta2/Neurod、Glut 2、Pax 6、巢蛋白、PDX-1、ngn 3、胰岛素和胰高血糖素）。免疫荧光法观察到胰岛素和C肽的共表达。此外，它们能够以葡萄糖依赖性方式释放胰岛素，并改善链脲佐菌素（STZ）治疗的裸鼠的糖尿病状况。这些结果表明，人骨髓间充质干细胞可能是一个可用的候选人，以克服胰岛移植的局限性。(C)2009年国际分化学会。由爱思唯尔有限公司出版。保留所有权利。
It was recently reported that pluripotent mesenchymal stem cells (MSCs) in rodent bone marrow (BM) have the capacity to generate insulin-producing cells (IPCs) in vitro. However, little is known about this capacity in human BM-MSCs. We developed a nongenetic method to induce human BM-MSCs to transdifferentiate into IPCs both phenotypically and functionally. BM-MSCs from 12 human donors were sequentially cultured in specially defined conditions. Their differentiation extent toward beta-cell phenotype was evaluated systemically. Specifically, after induction human BM-MSCs formed spheroid islet-like clusters containing IPCs, which was further confirmed by dithizone (DTZ) staining and electron microscopy. These IPCs expressed multiple genes related to the development or function of pancreatic beta cells (including NKX6.1, ISL-1, Beta2/Neurod, Glut2, Pax6, nestin, PDX-1, ngn3, insulin and glucagon). The coexpression of insulin and c-peptide was observed in IPCs by immunofluorescence. Moreover, they were able to release insulin in a glucose-dependent manner and ameliorate the diabetic conditions of streptozotocin (STZ)-treated nude mice. These results indicate that human BM-MSCs might be an available candidate to overcome limitations of islet transplantation. (C) 2009 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.