Mesenchymal Stem Cells Overexpressing CXCR4 Attenuate Remodeling of Postmyocardial Infarction by Releasing Matrix Metalloproteinase-9
| Autor: | Muhammad Ashraf, Ronald W. Millard, Yigang Wang, Xiaohong Wang, Tao Wang, Xi Yong Yu, Atif Ashraf, Guo-Chang Fan, Dongsheng Zhang, Tiemin Zhao, Bo Dai, Meifeng Xu, Wei Huang |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Receptors CXCR4 Angiogenesis Blotting Western Green Fluorescent Proteins Myocardial Infarction Matrix metalloproteinase Biology Mesenchymal Stem Cell Transplantation Green fluorescent protein Mice Original Research Reports Cell Movement In vivo medicine Animals Hypoxia Cells Cultured Basement membrane Microscopy Confocal Myocardium Mesenchymal stem cell Mesenchymal Stem Cells Cell migration Cell Biology Hematology Molecular biology Cell biology Mice Inbred C57BL Blot medicine.anatomical_structure Matrix Metalloproteinase 9 Echocardiography Female RNA Interference Developmental Biology |
| Zdroj: | Stem Cells and Development. 21:778-789 |
| ISSN: | 1557-8534 1547-3287 |
| Popis: | Myocardial infarction (MI) results in loss of myofibers in the ischemic zone of the heart, followed by scar formation. These factors increase barriers to mobilization of mesenchymal stem cells (MSC), thereby impeding their effectiveness in cardiac repair. This study examined MSC overexpressing CXCR4 (MSC(CX4)) to determine penetration into infarcted myocardium by releasing collagen degrading enzyme, matrix metalloproteinase-9 (MMP-9). In vitro, mouse MSC were utilized, including MSC using adenoviral transduction, to express CXCR4/green fluorescent protein (GFP) (MSC(CX4)), Null/GFP (MSC(Null)), MSC treated with siRNA targeting CXCR4 (MSC(siR)), MSC treated with control siRNA(MSC(Con-siR)), MSC(CX4) treated with siRNA targeting MMP-9 (MSC(CX4-siRMP9)) and MMP-14 (MSC(CX4-siRMP14)), MSC derived from MMP-9 knockout mouse with adenoviral transduction for GFP (MSC(MP9-)), or MSC(MP9-) plus overexpressing CXCR4 (MSC(MP9-CX4)). The ability to cross the basement membrane was evaluated in all MSC using a trans-collagen gel invasion assay. The CXCR4 and MMP expression were analyzed by Western blot. In vivo, MSC with various treatments were infused into mice via tail vein injections 7 days after MI. Echocardiography was performed before harvesting hearts for analysis at 4 weeks after MSC injection. Both in vitro and in vivo studies demonstrated upregulation of MMP-9 induced by MSC(CX4), promoting increased GFP(+) cell migration into the infarcted area in comparison to control group. This enhanced response was associated with reduced left ventricular (LV) fibrosis, increased LV free wall thickness, angiogenesis, and improved LV function. Under hypoxic conditions, MMP-9 is upregulated in MSC(CX4), thus facilitating cross of the basement membrane, resulting in an improved remodeling of post-MI tissue. |
| Databáze: | OpenAIRE |
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