Cellular cardiomyoplasty in large myocardial infarction: Can the beneficial effect be enhanced by ACE-inhibitor therapy?

Background: Cellular cardiomyoplasty with bone marrow derived stromal (MSC) and mononuclear (BMNC) cells has been shown to improve performance of infarcted hearts. We performed a comparative study with MSC and BMNC and tested the hypothesis that captopril treatment could enhance the beneficial effect of cell therapy in large myocardial infarctions. Methods: Male syngeneic Wistar rats underwent experimental infarction and were randomized to receive 1-3 x 10(6) MSC, 10(8) BMNC or vehicle (BSS group). Two additional groups were treated with captopril and received 1-3 x 10(6) MSC (Cap.MSC) or vehicle (Cap). Results: The ejection fraction (EF%) of MSC and BMNC-treated rats was higher than in the BSS rats, eight weeks after transplantation (33.0+/- 4.0, 34.0+/-2.0 and 20.0+/-2.0% respectively, P<0.01). Both captopril-treated groups improved EF% similarly. But only captopril plus MSC treatment almost restored cardiac function to control levels, 8 weeks after injection (60.50+/-5.40% vs. 41.00+/-4.50% in Cap.MSC and Cap respectively, P<0.05). Many DAPI-labelled cells were found in the scar tissue of the left ventricle only in the Cap.MSC group. Conclusions: Cell transplantation with both MSC and BMNC produced a similar stabilisation of heart function, but the success of the cell engraftment and the recovery of cardiac performance were dependent on concomitant treatment with captopril. (C) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.