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Can erythropoietin improve skeletal myoblast engraftment in infarcted myocardium?

^a INSERM U 633, Laboratoire d'Etude des Greffes et Prothèses Cardiaques, Hôpital Broussais; Assistance Publique-Hôpitaux de Paris, Ecole de Chirurgie, Paris, France
^b CHU G. Montpied, Department of Cardiology, Clermont-Ferrand, France
^c Clinical Investigation Center 9201, Assistance Publique-Hôpitaux de Paris/INSERM, Hôpital Européen Georges Pompidou, Paris, France
^d INSERM, U 652, Hôpital Broussais, Paris, France
^e Assistance Publique-Hô pitaux de Paris, Hôpital Européen Georges Pompidou, Department of Pathology; Université Paris Descartes, Faculté Médecine, Paris, France
^f Assistance Publique-Hô pitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiology; Université Paris Descartes, Faculté de Médecine, Paris, France
^g Assistance Publique-Hô pitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiovascular Surgery; Université Paris Descartes, Faculté de Médecine, Paris, France

*Corresponding author. Tel.: +33 1 56093622; fax: +33 1 56093261.

E-mail address: philippe.menasche{at}egp.aphp.fr (P. Menasché).

The benefits of skeletal myoblast transplantation are limited by the high rate of early cell death which is partly of ischemic origin. We, therefore, assessed whether graft survival could be improved by the additional use of the angiogenic cytokine erythropoietin (EPO). Thirty-five Lewis rats underwent coronary artery ligation and, two weeks later, were randomized to receive in-scar injections of control medium, skeletal myoblasts (5x10⁶) or skeletal myoblasts with EPO started the day before transplantation and continued for two weeks (500 U/kg three times a week). A fourth group was treated by EPO alone without injections. Function was assessed by 2D echocardiography before transplantation and one month thereafter. Compared with controls and hearts treated by EPO-alone, those transplanted with myoblasts yielded a significantly better recovery of LV ejection fraction, irrespective of whether they had received EPO or not. Neither the area of myoblast engraftment, nor angiogenesis differed between the myoblast-alone and the myoblast+EPO groups. Apoptosis was hardly detectable and, therefore, unaffected by EPO therapy. In this model, EPO failed to improve myoblast engraftment and postinfarction LV function. These negative findings justify to pursue the search for alternate cell survival-enhancing strategies.

Key Words: Stem cells; Myoblasts; Transplantation; Heart failure; Myocardial infarction

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