Characterization of long-term endogenous cardiac repair in children after heart transplantation.
OBJECTIVE
Circulating cells repopulate the heart at a very low rate in adult humans. The knowledge about time-dependent cardiac regeneration is very limited and the contribution of circulating cells to cardiomyocytes or vascular cells in children is unknown. This study investigates the endogenous repair capacity and the long-term incorporation of circulating cells in heart-transplanted children.


RESULTS
Cardiac and endothelial chimerism was detected in endomyocardial biopsies of nine children (age 1 months-14 years) with sex-mismatched heart transplantation by fluorescence in situ hybridization. Time from transplantation to biopsy ranged from 1 month up to 10 years. The extent of repopulating cardiomyocytes was 2.39 +/- 1.54% (range: 0-4.2%) and correlated significantly with the time from transplantation to biopsy sampling (r(2) = 0.69, P = 0.006; n = 9). The calculated contribution of male cardiomyocytes in the female heart per year was 0.36 +/- 0.09%. Consistent with the previous reports, the incorporation of vascular cells was higher compared with cardiomyocytes (14.4 +/- 4.17%), but did not correlate in a time-dependent manner.


CONCLUSIONS
Circulating cells contribute to cardiomyocytes and endothelial cells in children after heart transplantation. The incidence of repopulating cardiomyocytes continuously increases in a time-dependent manner ( approximately 4% Y-chromosome(+) cardiomyocytes/10 years) and resembles the cardiac regeneration activity observed in adults.
Department of Molecular Cardiology, Internal Medicine III, JW Goethe University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Stefan
S
Rupp
Masamichi
M
Koyanagi
Masayoshi
M
Iwasaki
Jürgen
J
Bauer
Susanne
S
von Gerlach
Dietmar
D
Schranz
Andreas M
AM
Zeiher
Stefanie
S
Dimmeler
D000293:Adolescent; D002454:Cell Differentiation / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006331:Heart Diseases / Q000503:physiopathology; D016027:Heart Transplantation / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008833:Microcirculation / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology; D010641:Phenotype; D012038:Regeneration / Q000502:physiology*; D012727:Sex Characteristics; D013234:Stem Cells / Q000166:cytology; D013997:Time Factors; D018183:Transplantation Chimera / Q000502:physiology