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Intracoronary bone marrow cell application for terminal heart failure in children

Published online by Cambridge University Press:  13 February 2012

Stefan Rupp
Affiliation:
Pediatric Heart Center, Justus-Liebig University Giessen, Giessen, Germany
Christian Jux
Affiliation:
Pediatric Heart Center, Justus-Liebig University Giessen, Giessen, Germany
Halvard Bönig
Affiliation:
German Red Cross Blood Service Baden–Württemberg–Hessen and Institute for Transfusion Medicine and Immunohaematology, Goethe University Frankfurt, Frankfurt, Germany
Jürgen Bauer
Affiliation:
Pediatric Heart Center, Justus-Liebig University Giessen, Giessen, Germany
Torsten Tonn
Affiliation:
German Red Cross Blood Service Baden–Württemberg–Hessen and Institute for Transfusion Medicine and Immunohaematology, Goethe University Frankfurt, Frankfurt, Germany
Erhard Seifried
Affiliation:
German Red Cross Blood Service Baden–Württemberg–Hessen and Institute for Transfusion Medicine and Immunohaematology, Goethe University Frankfurt, Frankfurt, Germany
Stefanie Dimmeler
Affiliation:
Department of Cardiology, Goethe University Frankfurt, Frankfurt, Germany
Andreas M. Zeiher
Affiliation:
Department of Cardiology, Goethe University Frankfurt, Frankfurt, Germany
Dietmar Schranz*
Affiliation:
Pediatric Heart Center, Justus-Liebig University Giessen, Giessen, Germany
*
Correspondence to: Professor Dr D. Schranz, MD, Pediatric Heart Center, Justus-Liebig University, Feulgenstrasse 12, 35385 Giessen, Germany. Tel: 049 641 9943461; Fax: 049 641 9943469; E-mail: [email protected]

Abstract

Introduction

In spite of tremendous progress in the medical and surgical treatment of children with congenital heart disease and dilated cardiomyopathy achieved during the past few decades, for some children a heart transplant remains the only option. Clinically relevant benefits of intracoronary injection of autologous stem cells on cardiac function and remodelling have been demonstrated in adult patients with acute myocardial infarction. Experience with autologous stem cell therapy in children with severe congenital or acquired pump failure is limited to a small number of case reports.

Method and results

Between 2006 and 2010, nine severely ill children were treated with intracoronary infusion of autologous bone marrow-derived mononuclear cells as part of a compassionate therapy in our centre. No procedure-related unexpected adverse events occurred. There was one patient on extracorporeal membrane oxygenation who died of haemorrhage unrelated to the procedure; three patients proceeded to heart transplantation once a donor heart became available. The other five patients showed an improvement with respect to New York Heart Association classification (greater than or equal to 1), brain natriuretic peptide serum levels, and ejection fraction.

Conclusion

Similar to adults, intracoronary injection of autologous bone marrow cell is technically feasible and safe for children. On the basis of our data, we propose to perform a pilot study for children with congestive heart failure, to formally assess the efficacy of intracoronary autologous bone marrow cell therapy.

Type
Original Article
Copyright
Copyright © Cambridge University Press 2012

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Footnotes

*

Institute for Transfusion Medicine, German Red Cross Blood Donor Service East, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany.

References

1.Pierpont, ME, Basson, CT, Benson, DW Jr, et al. Genetic basis for congenital heart defects: current knowledge: a scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation 2007; 115: 30153038.CrossRefGoogle Scholar
2.Arola, A, Tuominen, J, Ruuskanen, O, Jokinen, E. Idiopathic dilated cardiomyopathy in children: prognostic indicators and outcome. Pediatrics 1998; 101: 369376.CrossRefGoogle Scholar
3.Nugent, AW, Daubeney, PE, Chondros, P, et al. The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med 2003; 348: 16391646.CrossRefGoogle ScholarPubMed
4.Alvarez, J, Wilkinson, JD, Lipshultz, SE, for the Pediatric Cardiomyopathy Registry Study Group. Outcome predictors for pediatric dilated cardiomyopathy: a systematic review. Progress in Pediatric Cardiology 2007; 23: 2532.CrossRefGoogle ScholarPubMed
5.Almond, CS, Thiagarajan, RR, Piercey, GE, et al. Waiting list mortality among children listed for heart transplantation in the United States. Circulation 2009; 119: 717727.CrossRefGoogle ScholarPubMed
6.Anversa, P, Leri, A, Rota, M, et al. Concise review: stem cells, myocardial regeneration, and methodological artifacts. Stem Cells 2007; 25: 589601.CrossRefGoogle ScholarPubMed
7.Urbich, C, Dimmeler, S. Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 2004; 95: 343353.CrossRefGoogle ScholarPubMed
8.Hsieh, PC, Segers, VF, Davis, ME, et al. Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat Med 2007; 13: 970974.CrossRefGoogle ScholarPubMed
9.Rupp, S, Koyanagi, M, Iwasaki, M, et al. Characterization of long-term endogenous cardiac repair in children after heart transplantation. Eur Heart J 2008; 29: 18671872.CrossRefGoogle ScholarPubMed
10.Bergmann, O, Bhardwaj, RD, Bernard, S, et al. Evidence for cardiomyocyte renewal in humans. Science 2009; 324: 98102.CrossRefGoogle ScholarPubMed
11.Lange, R, Vogt, M, Horer, J, et al. Long-term results of repair of anomalous origin of the left coronary artery from the pulmonary artery. Ann Thorac Surg 2007; 83: 14631471.CrossRefGoogle ScholarPubMed
12.Strauer, BE, Brehm, M, Zeus, T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002; 106: 19131918.CrossRefGoogle ScholarPubMed
13.Assmus, B, Schachinger, V, Teupe, C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 2002; 106: 30093017.CrossRefGoogle ScholarPubMed
14.Fernandez-Aviles, F, San Roman, JA, Garcia-Frade, J, et al. Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circ Res 2004; 95: 742748.CrossRefGoogle ScholarPubMed
15.Wollert, KC, Meyer, GP, Lotz, J, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004; 364: 141148.CrossRefGoogle ScholarPubMed
16.Schachinger, V, Erbs, S, Elsasser, A, et al. Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 2006; 355: 12101221.CrossRefGoogle ScholarPubMed
17.Lunde, K, Solheim, S, Aakhus, S, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006; 355: 11991209.CrossRefGoogle ScholarPubMed
18.Abdel-Latif, A, Bolli, R, Tleyjeh, IM, et al. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med 2007; 167: 989997.CrossRefGoogle ScholarPubMed
19.Lipinski, MJ, Biondi-Zoccai, GG, Abbate, A, et al. Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials. J Am Coll Cardiol 2007; 50: 17611767.CrossRefGoogle ScholarPubMed
20.Rupp, S, Bauer, J, Tonn, T, et al. Intracoronary administration of autologous bone marrow-derived progenitor cells in a critically ill two-yr-old child with dilated cardiomyopathy. Pediatr Transplant 2009; 13: 620623.CrossRefGoogle Scholar
21.Rupp, S, Zeiher, AM, Dimmeler, S, et al. A regenerative strategy for heart failure in hypoplastic left heart syndrome: intracoronary administration of autologous bone marrow-derived progenitor cells. J Heart Lung Transplant 2010; 29: 574577.CrossRefGoogle ScholarPubMed