Bone marrow cells and cardiac repair

Mailing Address: Piero Anversa, M.D. • Vosburgh Pavilion, Room 302, New York Medical College, Valhalla, NY 10595 E-mail: piero_anversa@nymc.edu Understanding the mechanisms by which adult somatic stem cells are capable of improving cardiac function in ischemic heart disease is of fundamental biological and clinical importance1. Endothelial progenitor cells and mononuclear bone marrow cells have been administered to patients affected by acute and chronic ischemic heart failure2. These interventions have had positive outcome documenting not only the feasibility and safety of this therapeutic approach but also benefi cial effects on ventricular performance. The study in the current issue of the Arquivos Brasileiros de Cardiologia unexpectedly documents that intracoronary injection of bone marrow mononuclear cells to patients suffering from Chagas cardiomyopathy is safe and may have a favorable impact on the late evolution of the cardiac disease3. The trial included 28 patients with congestive heart failure due to infection by Trypanosoma cruzi. The cell treatment resulted in improvement in ejection fraction and functional NYHA class, together with amelioration of quality of life and increased walked distance. The pathology of Chagas cardiomyopathy differs significantly from post-infarction myopathy4; it is characterized by diffuse myocardial scarring and chronic cellular infi ltrates composed of lymphocytes, plasma cells and macrophages, which indicate an ongoing active process with continuous loss of myocytes and activation of connective tissue cells and collagen deposition. These structural abnormalities of the myocardium complicate further the interpretation of the potential therapeutic effi cacy of bone marrow cells (BMCs) in Chagas disease. Experimental studies in animal model of ischemic cardiomyopathy have raised several questions concerning the multiple variables involved in cardiac repair after BMC implantation5,6. And these factors apply to the management of Chagas disease as well. They include (a) the number of therapeutically effective cells which are administered, (b) the magnitude of cell death and survival of the BMCs in the hostile milieu of the damaged region of the heart, (c) the extent of BMC engraftment, and, fi nally, (d) the degree of growth and differentiation of the homed BMCs. An additional critical variable of BMCs is their level of plasticity, which is dictated by their ability to acquire the myocyte, and vascular smooth muscle and endothelial cell lineages7. Importantly, the injected BMCs can contribute indirectly to cardiac regeneration by releasing a variety of peptides that exert a paracrine action on the myocardium8 and its resident cardiac progenitor cells (CPCs)9. These mechanisms are not mutually exclusive and bone marrow progenitor cells may participate directly and indirectly in the repair process. In all cases, however, progenitor cells have to engage themselves in homing into the myocardium in order to perform specifi c functions. These biological processes depend on a successful interaction between progenitor cell classes and tissue microenvironment10. Although the clinical trial performed by Vilas-Boas and collaborators projects an unprecedented implication of stem cell therapy for the damaged heart3, the issues raised above will have also to be addressed in Chagas disease to acquire a biological understanding of the function of BMCs in this cardiomyopathy.