Human bone marrow mesenchymal stem cells differentiate into insulin-producing cells upon microenvironmental manipulation in vitro

被引:132
作者
Xie, Qiu-Ping [1 ]
Huang, Hai [1 ]
Xu, Bin [1 ]
Dong, Xin [1 ]
Gao, Shun-Liang [1 ]
Zhang, Bo [1 ]
Wu, Yu-Lian [1 ]
机构
[1] Zhejiang Univ, Affiliated Hosp 2, Dept Surg, Sch Med, Hangzhou 310009, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Islet/transplantation; Mesenchymal stem cells; Differentiation; Human bone marrow; Diabetes; PANCREATIC BETA-CELLS; PROGENITOR CELLS; STROMAL CELLS; ISLET TRANSPLANTATION; TRANS-DIFFERENTIATION; VIVO; EXPANSION; RAT; REGENERATION; GENERATION;
D O I
10.1016/j.diff.2009.01.001
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:483 / 491
页数:9
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