期刊
DIFFERENTIATION
卷 77, 期 5, 页码 483-491出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.diff.2009.01.001
关键词
Islet/transplantation; Mesenchymal stem cells; Differentiation; Human bone marrow; Diabetes
资金
- National Natural Science Foundation of China [30471697, 30672072]
- Natural Science Foundation of Zhejiang Province, China [Z204033, Y206247]
- Foundation of Science and Technology Department of Zhejiang Province, China [2006C23G2010216]
- Ministry of Science and Technology of People's Republic of China [2007AA02Z476]
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.
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