Abstract
AIMS: Stem cell recruitment into the heart is determined by a concentration gradient of stromal-derived factor 1 (SDF-1) from bone marrow to peripheral blood and from blood to injured myocardium. However, this gradient is decreased in chronic myocardial infarction (MI). This study evaluated the effect of cell therapy using bone marrow stromal cells (BMSCs) on an SDF-1 gradient in post-infarction rabbits. METHODS AND RESULTS: Myocardial infarction was induced in male New Zealand white rabbits (2.5-3 kg) by ligation of the left anterior descending coronary artery. Two months later, the rabbits were randomized to either saline or BMSC (2 x 10(6) autologous BMSCs injected into the left ventricular cavity) treatment. Four weeks after therapy, the SDF-1 gradients from bone marrow to blood and from blood to myocardium increased in the BMSC group compared with the saline group. This was accompanied by an increase in cells positive for CD34, CD117, and STRO-1 in the myocardium, resulting in more capillary density, better cardiac function, and a decrease in infarct size. CONCLUSION: Generation of an SDF-1 gradient towards the heart is a novel effect of BMSC-based cell therapy. This effect facilitates stem cell recruitment into remodelled myocardium and supports improvement in cardiac function.