Mesenchymal Stem Cells Overexpressing CXCR4 Attenuate Remodeling of Postmyocardial Infarction by Releasing Matrix Metalloproteinase-9

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 (MSCCX4) 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) (MSCCX4), Null/GFP (MSCNull), MSC treated with siRNA targeting CXCR4 (MSCsiR), MSC treated with control siRNA(MSCCon-siR), MSCCX4 treated with siRNA targeting MMP-9 (MSCCX4-siRMP9) and MMP-14 (MSCCX4-siRMP14), MSC derived from MMP-9 knockout mouse with adenoviral transduction for GFP (MSCMP9−), or MSCMP9− plus overexpressing CXCR4 (MSCMP9-CX4). The ability to cross the basement membrane was evaluated in all MSC using a trans-collagen gel invasion ass...