Evidence for ischemia induced host-derived bone marrow cell mobilization into cardiac allografts

Abstract

Mobilized bone marrow stem cells (BMSC) exhibit high degree of plasticity and participate in the repair process in the event of myocardial damage. In this study, we verified the proportional contribution of recipient BMSC in the repair process and identified their specific surface markers. Wild-type (WT) donor female heart was transplanted into abdominal cavity of male rat (Group I). In some of recipient animals, infarction was created by LAD occlusion (Group II). Two weeks later, transplanted female hearts were harvested for histological analysis of the mobilized cells. C-kit, CD31, Ki67 and Y-chromosome were used as markers to identify mobilized cells in the female hearts. Y-chromosome positive cells were found in the donor female cardiac allografts. Acute myocardial infarction (AMI) of recipient heart induced migration of progenitor cells into the lesions of chronic rejection in the allograft. Donor ventricular mass reduction was more pronounced in Group I. Endothelial progenitor cells induced by AMI from male recipient extensively migrated into the cardiac allograft. SDF-1 mRNA levels significantly increased (peak level at 24 h after AMI) in recipient heart. CXCR4 was strongly expressed in the transplanted hearts around the perivascular area. Spontaneous mobilization of hematopoietic progenitor cells (HPCs) occurred in cardiac allografts after creating recipient heart AMI and was detectable until 2 weeks. These data suggests that CXCR4 overexpression enhances vascularization in the damaged myocardium and SDF-1/CXCR4 axis seems particularly important in progenitor cell chemotaxis, homing, engraftment and retention in damaged myocardium. In addition, BMSC attracted to the site of ischemic injury participate in cardiac repair.