title: Cellular repopulation of myocardial infarction in patients with sex-mismatched heart transplantation.
abstract: OBJECTIVE
  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.
  
  
  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 male cardiomyocytes and their increase in infarcted regions to 0.07% was not significant.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology and Pneumology, Georg-August-University Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany. elisabeth.hoecht@med.uni-goettingen.de
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Höcht-Zeisberg
authors.forename: Henning
authors.initials: H
authors.lastname: Kahnert
authors.forename: Kaomei
authors.initials: K
authors.lastname: Guan
authors.forename: Gerald
authors.initials: G
authors.lastname: Wulf
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmerlein
authors.forename: Thilo
authors.initials: T
authors.lastname: Schlott
authors.forename: Gero
authors.initials: G
authors.lastname: Tenderich
authors.forename: Reiner
authors.initials: R
authors.lastname: Körfer
authors.forename: Ute
authors.initials: U
authors.lastname: Raute-Kreinsen
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuss
mesh_terms: D000368:Aged; D001344:Autopsy; D002454:Cell Differentiation; D041322:Chromosomes, Human, Y; D005260:Female; D016027:Heart Transplantation / Q000379:methods / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000473:pathology* / Q000601:surgery; D032383:Myocytes, Cardiac / Q000473:pathology*; D012680:Sensitivity and Specificity; D012737:Sex Factors; D013234:Stem Cells / Q000473:pathology; D016019:Survival Analysis