Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance

Abstract

With the goal of devising a non-invasive cell therapy for cardiac repair that may be well tolerated by patients with myocardial infarction (MI), this study evaluated the efficacy of intravenous infusion of genetically modified mesenchymal stem cells (MSCs) overexpressing CXC chemokine receptor 4 (CXCR4). CXCR4 is the cognate receptor for stromal-derived factor-1 (SDF-1), a chemokine required for homing of progenitor cells to ischemic tissues. In this study, retrovirally transduced MSCs constitutively expressing CXCR4 (CXCR4-MSCs) were delivered intravenously 24 hours after coronary occlusion/reperfusion in rats. When compared with untransduced MSCs, CXCR4-MSCs homed in toward the infarct region of the myocardium in greater numbers. In the CXCR4-MSC-treated animals, echocardiographic imaging 30 days after MI showed a decrease in anterior wall thinning and good preservation of left ventricular (LV) chamber dimensions, whereas the animals treated with saline or unmodified MSCs showed significant remodeling. Histochemical analysis showed a decrease in collagen I/III ratio in the infarcted wall of CXCR4-MSC-treated animals, thereby suggesting improved chamber compliance. Assessment revealed post-MI recovery of LV function in the CXCR4-MSC-treated animals, whereas LV function remained depressed in the saline and MSC-treated animals. In summary, intravenous delivery of genetically modified MSCs expressing CXCR4 may be a useful, non-invasive, and safe therapeutic strategy for post-infarction myocardial repair.