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J Thorac Cardiovasc Surg 2006;132:1321-1328
© 2006 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Combined transplantation of skeletal myoblasts and angiopoietic progenitor cells reduces infarct size and apoptosis and improves cardiac function in chronic ischemic heart failure

Nikolaos Bonaros, MDa,*, Rauend Rauf, MDa, Dominik Wolf, MDb, Eva Margreiter, PhDd, Alexandar Tzankov, MDc, Bernhard Schlechta, MDe, Alfred Kocher, MDe, Harald Ott, MDa, Thomas Schachner, MDa, Steffen Hering, PhDf, Johannes Bonatti, MDa, Guenther Laufer, MDa

a Department of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria
b Department of Hematology, Innsbruck Medical University, Innsbruck, Austria
c Department of Pathology, Innsbruck Medical University, Innsbruck, Austria
d Innovacell Biotechnology, Innsbruck, Austria
e Department of Cardiothoracic Surgery, Vienna Medical University, Vienna, Austria
f Institute of Pharmacology and Toxicology, University of Vienna, Vienna, Austria.

Received for publication March 23, 2006; accepted for publication July 7, 2006.

* Address for reprints: Nikolaos Bonaros, MD, Department of Cardiac Surgery, Innsbruck Medical University, Anichstrasse 35, A-6020, Innsbruck, Austria (Email: nikolaos.bonaros{at}uibk.ac.at).

OBJECTIVES: Cellular cardiomyoplasty using skeletal myoblasts or angiopoietic progenitor cells offers a promising approach for the treatment of ischemic heart failure. Although several studies have shown encouraging results in acute myocardial infarction, the efficacy of cell therapy using skeletal myoblasts and angiopoietic progenitor cells in chronic ischemic heart disease remains undetermined.

METHODS: Ischemic heart failure was induced by left anterior descending coronary artery ligation in nude rats: (1) Culture medium, (2) homologous skeletal myoblasts (SM), (3) human AC-133+ cells (SC), and (4) both skeletal myoblasts and AC-133+ cells (Comb) were injected in the infarct (SM) and peri-infarct area (SC) 4 weeks after infarction. Assessment of myocardial function included echocardiography 4 weeks after cell delivery. Histology was based on quantification of myocardial fibrosis, apoptosis, and capillary density.

RESULTS: Left ventricular dilatation was attenuated and ejection fraction improved significantly after cell transplantation (SM: 59.4% ± 8.8%, SC: 60.3% ± 6.6%, Comb: 68.2% ± 5.6% vs control: 41.5% ± 7.4%, P = .0013). Quantification of scar tissue showed a significant reduction of infarct area in cell-treated animals (SM: 22.3% ± 9.1%, SC: 19.8% ± 7.6%, Comb: 13.2% ± 5.8% vs controls: 36.5% ± 8.2%, P = .008). Improvement of myocardial function was associated with reduced apoptotic index (SM: 3.2% ± 0.9%, SC: 3.1% ± 0.6%, Comb: 1.8% ± 0.8% vs controls: 10.3% ± 1.6%, P = .0002) and increased vascular density (SM: 5.2 ± 1.2, SC: 8.3 ± 1.8, Comb: 12.3 ± 2.3, controls: 1.9 ± 0.3, all capillary vessels/high-power field, P = .007) in animals after cellular cardiomyoplasty.

CONCLUSIONS: Combined transplantation of skeletal myoblasts and angiopoietic progenitor cells results in ventricular function improvement, reduction of scar size and myocardial apoptosis, and increased neoangiogenesis in chronic ischemia. Clinical studies are warranted to prove this new therapeutic concept.

Abbreviations and Acronyms LVEDD = left ventricular end-diastolic diameter; LVEF = left ventricular ejection fraction; TUNEL = deoxyuride-5'-triphosphate biotin nick end labeling; VEGF = vascular endothelial growth factor; YFP = yellow fluorescent protein




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N. Bonaros, R. Rauf, E. Werner, B. Schlechta, E. Rohde, A. Kocher, J. Bonatti, and G. Laufer
Neoangiogenesis after combined transplantation of skeletal myoblasts and angiopoietic progenitors leads to increased cell engraftment and lower apoptosis rates in ischemic heart failure
Interactive CardioVascular and Thoracic Surgery, April 1, 2008; 7(2): 249 - 255.
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