期刊
CELLULAR IMMUNOLOGY
卷 281, 期 1, 页码 68-75出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2013.02.001
关键词
Mesenchymal stem cells; Migration; Notch signaling; CXCR4
资金
- National Natural Science Foundation of China [30830067, 81030010, 81072972, 30873229]
- Ministry of Science and Technology of China [2009CB5 21706, 2011ZXJ09101-02C]
Mesenchymal stem cells (MSCs) have been used to repair injured tissues through immune-suppression and/or cell replace mechanisms. However, a significant barrier to MSC therapy is insufficient MSC engraftment in injured tissues after systemic administration. Here, we report that cell surface, total protein, and mRNA levels of CXCR4 were significantly increased in MSCs when Notch signaling was interrupted by gamma-secretase inhibitor (GSI) or knockout of the transcription factor RBP-J, which mediates signaling from all four mammalian Notch receptors. The GSI-treated or RBP-J deficient MSCs showed stronger migration toward stromal cell-derived factor-1 alpha (SDF-1 alpha) than that of the control. In a mouse hepatic ischemia/reperfusion model, RBP-J deficient MSCs migrated into the injured liver tissues at a significantly higher efficiency than that of the control MSCs. Mice transfused with RBP-J deficient MSCs showed reduced liver damage. Therefore, Notch signaling regulates MSC migration and function, at least partially via the modulation of CXCR4 expression. (c) 2013 Elsevier Inc. All rights reserved.
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