Bone marrow stem cell therapy for cardiac repair: challenges and perspectives

Bone marrow (BM) stem cells can differentiate into multiple cell types, including vascular cells and, possibly, cardiac myocytes. Stem and progenitor cells are mobilized into the peripheral circulation early after myocardial infarction. Experimental evidence suggests that BM-derived cells injected into infarcted hearts can improve cardiac function. However, mechanisms underlying functional improvements remain unclear. Initial randomized, placebo-controlled trials in patients with acute myocardial infarction have provided controversial

On the one hand, a modest but significant and sustained improvement in left ventricular function was observed in the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) study contributing to the better clinical course. Results of other studies were neutral. Differences in the study design, cell processing or timing of cell delivery might explain, in part, different outcomes among studies. Furthermore, studies in patients with chronic ischemic heart disease remain observational, and therapeutic effects using surrogate end-points needs to be demonstrated. Thus, there is a need for further coordinated research with well designed, hypothesis-driven clinical trials, in parallel with fundamental research aimed at understanding the mechanisms underlying the biological and functional effects of BM cell therapy for cardiac repair.