Cellular repopulation of myocardial infarction in patients with sex-mismatched heart transplantation

Abstract

Aims Recent studies have suggested that human extracardiac progenitor cells are capable of differentiating into cardiomyocytes. In animal studies, myocardial infarction attracted bone marrow stem cells and enhanced their differentiation into cardiomyocytes. Based on these findings, we hypothesised that myocardial infarction stimulates the invasion of progenitor cells and their differentiation into endothelial and cardiac cells in the human heart. Methods and results We compared autopsy samples from male control patients who had received a female donor heart with samples from such patients who developed myocardial infarction after transplantation. Fluorescence in situ hybridisation (FISH) for detection of the Y-chromosome was combined with immunofluorescence staining for CD45 and CD68 to distinguish host-derived inflammatory cells. Additionally, we used a 3D-confocal imaging technique to indisputably assign Y-chromosome-positive nuclei to their cytoplasm. In patients with myocardial infarction after heart transplantation (n = 5), host-derived non-inflammatory progenitor and endothelial cells were significantly increased compared to non-infarcted patients (n = 9). Yet, by using this novel multi-step approach, only 0.02% of all. cells were estimated to be mate cardiomyocytes and their increase in infarcted regions to 0.07% was not significant. Conclusion Myocardial infarction enhances the invasion of extracardiac progenitor cells and their regeneration of endothelial cells. However, a significant differentiation into cardiomyocytes as a physiological mechanism of postischaemic regeneration does not occur in transplanted patients. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.