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Eur J Cardiothorac Surg 2005;27:1017-1021
© 2005 Elsevier Science NL

Intramyocardial microdepot injection increases the efficacy of skeletal myoblast transplantation

^a Center for Cardiovascular Repair, University of Minnesota, 312 Church Street, 55455 Minnesota, MN, USA
^b Department of Cardiac Surgery, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
^c Department of Biochemical Pharmacology, University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
^d Department of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, 1090 Wien, Austria

Received 13 September 2004; received in revised form 5 January 2005; accepted 20 January 2005.

^* Corresponding author. Tel.: +1 612 819 8228; fax: +1 612 626 1121. (E-mail: h.c.ott{at}aon.at).

Objective: Recent progress in the field of cellular cardiomyoplasty has opened new prospects for the treatment of ischemic heart disease and currently moves from bench to bedside. The aim of the present study was to develop a novel cell delivery technique, reducing target tissue damage and improving cell dispersion and engraftment. Methods: In 30 male Fischer F344 rats an infarction of the left ventricle was generated by ligation of the left anterior descendent artery. Seven days after infarction, either 15 microdepots of 10µl myoblast cell suspension (microdepot group) or culture medium (control group) were injected into the infarcted region using an automatic pressure injection device, or three depots of 50µl myoblast cell suspension (macrodepot group) were injected using the standard surgical technique. Echocardiography was performed in all rats before and 6 weeks after cell injection. In all groups the perioperative mortality was below 20%. Six weeks after cell transplantation, a significant improvement of ejection fraction was seen in both myoblast treated groups compared to controls (macrodepot, microdepot, control; 53.7±11.9, 70.7±2.0, 39.1±6.4; P=0.026, P<0.001). The microdepot group showed a more decent improvement than the macrodepot group (70.7±2.0 vs. 53.7±11.9, P=0.013). In both treated groups, grafted myoblasts differentiated into multinucleated myotubes within host myocardium, however, the engraftment pattern was different and angiogenesis was enhanced in the microdepot group. Conclusions: Intramyocardial multisite pressure injection allows the safe and reliable transplantation of several myoblast microdepots into an infarcted myocardium and improves the efficacy of myoblast transplantation compared to the standard technique.

Key Words: Stem cell • Heart • Myocardial infarction • Cellular cardiomyoplasty • Myoblast • Delivery

Abbreviations: LVEF = left ventricular ejection fraction • vWF = von Willebrand Factor • LVEDD = left ventricular enddiastolic diameter • VEGF = vascular endothelial growth factor

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