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Publication : Notch signaling regulates CXCR4 expression and the migration of mesenchymal stem cells.

First Author  Xie J Year  2013
Journal  Cell Immunol Volume  281
Issue  1 Pages  68-75
PubMed ID  23474530 Mgi Jnum  J:194910
Mgi Id  MGI:5475049 Doi  10.1016/j.cellimm.2013.02.001
Citation  Xie J, et al. (2013) Notch signaling regulates CXCR4 expression and the migration of mesenchymal stem cells. Cell Immunol 281(1):68-75
abstractText  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-1alpha (SDF-1alpha) 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.
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