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Eur J Cardiothorac Surg 2004;25:627-634
© 2004 Elsevier Science NL

Combined transplantation of skeletal myoblasts and bone marrow stem cells for myocardial repair in rats

^a Department of Cardiac Surgery, University of Innsbruck, Anichstrasse, A-6020 Innsbruck, Austria
^b Biochemical Pharmacology, University of Innsbruck, Innsbruck, Austria
^c Department of Hematology, University of Innsbruck, Innsbruck, Austria
^d Pharmacology and Toxicology, University of Vienna, Vienna, Austria

Received 13 September 2003; received in revised form 3 December 2003; accepted 15 December 2003.

^* Corresponding author. Tel.: +43-512-504-2501; fax: +43-512-504-2502
e-mail: h.c.ott{at}aon.at

Objectives: To prove whether intramyocardial transplantation of combined skeletal myoblasts (SM) and mononuclear bone marrow stem cells is superior to the isolated transplantation of these cell types after myocardial infarction in rats. Methods: In 67 male Fischer rats myocardial infarction was induced by direct ligature of the LAD. Seven days postinfarction baseline echocardiography and intramyocardial cell transplantation were performed. Via lateral thoracotomy 200 µl containing either 10⁷ SMs or 10⁷ bone marrow-derived mononuclear cells (BM-MNC) or a combination of 5x10⁶ of both cell types (MB) were injected in 10–15 sites in and around the infarct zone. In controls (C) 200 µl of cell-free medium were injected in the same manner. Before injection both cell types were stained using a fluorescent cell linker kit (PKH, Sigma). In addition, SMs were transfected with green fluorescent protein. Nine weeks postinfarction follow-up echocardiography was performed and animals were sacrificed for further analysis. Results: At baseline echocardiography there was no difference in left ventricular ejection fraction (LVEF; C, SM, BM-MNC, MB: 60.1±3.2, 53.3±10.2, 53.1±8.7, 49±9.0%) and left ventricular end diastolic diameter (LVEDD; C, SM, BM-MNC, MB: 6.5±0.8, 5.17±0.8, 5.77±1.4, 6.25±0.8 mm) between the different therapeutic groups. Eight weeks after cell transplantation LVEDD was significantly increased in all animals except those that received a combination of myoblasts and bone marrow stem cells (MB; C, SM, BM-MNC, MB: 7.7±0.6 mm, P=0.001; 7.7±1.5 mm, P<0.001; 7.7±1.1 mm, P=0.005; 6.6±1.7 mm, P=0.397). At the same time LVEF decreased significantly in the control group (C), stayed unchanged in animals that received bone marrow stem cells (BM-MNC) and increased in animals that received myoblasts (SM) and a combination of both cell types (MB; C, SM, BM-MNC, MB: 45.3±7.0%, P=0.05; 63.9±15.4%, P=0.044; 54.3±6.3%, P=0.607; 63.0±11.5%, P=0.039). Conclusions: The present data show that the concept of combining SMs with bone marrow-derived stem cells may be of clinical relevance by merging the beneficial effects of each cell line and potentially reducing the required cell quantity. Further studies are required to identify the exact mechanisms underlying this synergy and to allow full exploitation of its therapeutic potential.

Key Words: Cellular cardiomyoplasty • Skeletal myoblast • Bone marrow • Cell transplantation • Cardiomyopathy

Abbreviations: BM-MNC, bone marrow-derived mononuclear cell • IVS, interventricular septum • LVEDD, left ventricular end diastolic diameter • LVEF, left ventricular ejection fraction • SM, skeletal myoblast • vWF, von Willebrand Factor

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