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European Heart Journal Advance Access published online on May 28, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn223
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Characterization of long-term endogenous cardiac repair in children after heart transplantation

Stefan Rupp1,2, Masamichi Koyanagi1, Masayoshi Iwasaki1, Jürgen Bauer2, Susanne von Gerlach3, Dietmar Schranz2, Andreas M. Zeiher1 and Stefanie Dimmeler1,*

1 Department of Molecular Cardiology, Internal Medicine III, J.W. Goethe University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
2 Pediatric Heart Center, University of Giessen and Marburg, 35390 Giessen, Germany
3 Department of Pathology, University of Giessen and Marburg, 35385 Giessen, Germany

Received 1 January 2008; revised 1 May 2008; accepted 6 May 2008.

* Corresponding author. Tel: +49 69 6301 7440, Fax: +49 69 6301 7113, Email: dimmeler{at}em.uni-frankfurt.de

Aims: 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.

Methods and 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 (r2 = 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.

Conclusion: 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 (~4% Y-chromosome+ cardiomyocytes/10 years) and resembles the cardiac regeneration activity observed in adults.

Key Words: Heart failure • Cardiac regeneration • Cardiac chimerism • Progenitor cells


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