Despite the improvement of pharmacological and surgical therapies, the mortality related to ischemic heart failure remains high. During the last years, bone marrow-mesenchymal stem cell (BM-MSC) therapy has been proposed as a novel approach for the prevention and therapy of heart failure. Intramyocardial injection allows concentration of grafted cells within the injured zone. However, a major problem of with intraparenchymal route of administration is the early death of most of grafted cells. The goal of the MESAMI program is to evaluate the effect of intramyocardial administration of BM-MSC preconditioned or not with the pineal hormone melatonin in ischemic cardiomyopathy.

Our preclinical investigations have designed a preconditioning strategy of BM-MSCs with the melatonin that significantly increases survival and efficacy of grafted cells in animal models of myocardial ischemia. Melatonin treatment significantly ameliorates the beneficial effects of BM-MSC on the recovery of cardiac function. In the mean time, we started a phase I clinical trial in patients with severe ischemic cardiomyopathy and no option of revascularization, using the NOGA XP system to guide injections into the myocardium. Based on our basic research results, we are developing a multicenter phase II trial on the effects of intramyocardial administration of melatonin-preconditioned BM-MSC in patients with chronic ischemic cardiomyopathy.

The ongoing MESAMI program is representative of a translational research program in France.