[Cell therapy: results in Cardiology].
Cell therapy is already a clinical reality, having restored function to postinfarct akinetic myocardial scars. Ongoing trials are testing skeletal myoblasts in patients with chronic left ventricular dysfunction, and bone marrow-derived cells are being tried in patients with acute myocardial infarction undergoing concomitant percutaneous revascularization by angioplasty and stenting. While these procedures appear to be safe, their efficacy is uncertain. Indeed, the enthusiasm generated by the first phase I studies has been tempered by the less successful outcomes of recently published randomised controlled phase II trials. At least these studies have the merit of highlighting two major issues--the modest efficiency of cell transfer and the high rate of posttransplantation cell death--which need to be addressed if cell therapy is to hold its promise. Furthermore, it is becoming clear that the plasticity of adult somatic cells is likely to be much more limited than initially thought, and that the generation of new cardiomyocytes capable of ensuring true myocardial regeneration is still elusive. So far the documented effects of cell therapy are mainly due to aparacrine signaling action on the extracellular matrix, angiogenesis, or even recruitment of endogenous cardiac stem cells. Neither skeletal myoblasts nor bone marrow-derived cells meet the criteria required for true myocardial regeneration, i.e., electrical coupling between donor and recipient cells, leading to the formation of a syncytium and allowing the graft to beat in synchrony with the remainder of the heart and, thus, to effectively contribute to its pump function. We must therefore continue to explore other paths, notably using embryonic stem cells. If appropriately precommitted towards a cardiac lineage, these cells can diferentiate into cardiomyocytes following engraftment into postinfarct scars, leading to improved left ventricular function. Although several hurdles stand in the way of routine clinical applications, there are serious reasons for hoping that these cells will eventually provide an effective means of repairing diseased myocardial tissue.
Menasché
Philippe
P
Chirurgie cardiovasculaire, Hôpital Européen Georges Pompidou, 20, rue Leblanc--75908 Paris, Université Paris Descartes, Inserm U633, Paris.
D016026:Bone Marrow Transplantation; D002318:Cardiovascular Diseases / Q000628:therapy*; D006801:Humans; D018919:Neovascularization, Physiologic; D033581:Stem Cell Transplantation