Cellular cardiomyoplasty: improvement of left ventricular function correlates with the release of cardioactive cytokines

¹ Department of Medicine III, Martin-Luther-University, Halle, Germany; Institute of Physiological Chemistry, Martin-Luther-University, Halle, Germany
² Institute of Physiological Chemistry, Martin-Luther-University, Halle, Germany
³ Department of Medicine III, Martin-Luther-University, Halle, Germany
⁴ Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany
⁵ Institute of Physiological Chemistry, Martin-Luther-University, Halle, Germany; Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany
⁶ Institute for Cell Culture Technlogy, University of Bielefeld, Bielefeld, Germany

^* To whom correspondence should be addressed. E-mail: thomas.braun{at}kerckhoff.mpg.de.

	Abstract

A growing number of studies are reporting beneficial effects of the transplantation of alleged cardiac stem cells into diseased hearts after myocardial infarction. The mechanisms, however, by which transplanted cells might help to promote repair of cardiac tissue are not understood and might involve processes different from the differentiation of transplanted cells into cardiomyocytes. We have compared the effects exerted by skeletal myoblasts (which are not able to form new cardiomyocytes) and ES cell-derived cardiomyocytes after implantation into infarcted mouse hearts by echocardiographic follow-up and histological analysis and related these effects to the release of cardioactive cytokines. We found that both cell types led to a long lasting improvement of LV (left ventricle) function and to an improvement of tissue architecture. Since no relevant amounts of myoblast-derived cells were present in infarcted hearts 28 days after transplantation we investigated the release of cytokines from implanted cells both before and after transplantation into infarcted hearts. ES cell-derived cardiomyocytes and myoblasts secreted substantial amounts of IL-1, IL-6, TNF-, and oncostatin M (OSM), which strongly supported survival and protein synthesis of cultured cardiomyocytes. Conclusion: We postulate that the beneficial effects of the transplantation of myoblasts and cardiomyocytes on heart function and morphology do only partially (if at all) depend on the integration of transplanted cells into the myocardium but on the release of a complex blend of cardioactive cytokines.

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