Key Success Factors for Regenerative Medicine in Acquired Heart Diseases

Abstract Stem cell therapy offers a breakthrough opportunity for the improvement of ischemic heart diseases. Numerous clinical trials and meta-analyses appear to confirm its positive but variable effects on heart function. Whereas these trials widely differed in design, cell type, source, and doses reinjected, cell injection route and timing, and type of cardiac disease, crucial key factors that may favour the success of cell therapy emerge from the review of their data. Various types of cell have been delivered. Injection of myoblasts does not improve heart function and is often responsible for severe ventricular arrythmia occurrence. Using bone marrow mononuclear cells is a misconception, as they are not stem cells but mainly a mix of various cells of hematopoietic lineages and stromal cells, only containing very low numbers of cells that have stem cell-like features; this likely explain the neutral results or at best the modest improvement in heart function reported after their injection. The true existence of cardiac stem cells now appears to be highly discredited, at least in adults. Mesenchymal stem cells do not repair the damaged myocardial tissue but attenuate post-infarction remodelling and contribute to revascularization of the hibernated zone surrounding the scar. CD34+stem cells - likely issued from pluripotent very small embryonic-like (VSEL) stem cells - emerge as the most convincing cell type, inducing structural and functional repair of the ischemic myocardial area, providing they can be delivered in large amounts via intra-myocardial rather than intra-coronary injection, and preferentially after myocardial infarct rather than chronic heart failure.