Remote ischemic postconditioning enhances cell retention in the myocardium after intravenous administration of bone marrow mesenchymal stromal cells

Abstract Efficacy of intravenous administration of mesenchymal stromal cells (MSCs) for myocardial infarction (MI) is limited by low cell retention in the damaged myocardium. Previous studies indicated that remote ischemic conditioning could protect against ischemia–reperfusion-induced injury by release of various cytokines including stromal cell derived factor-1 alpha (SDF-1α). However, whether remote ischemic postconditioning (RIPostC) can also enhance the retention of infused cells in the myocardium by activating MSC homing is unclear. In this study, RIPostC was induced with 4 cycles of 5 min occlusion and reperfusion of the abdominal aorta in female Sprague–Dawley (SD) rats which underwent ligation of the coronary artery 1 week previously. Cytokine levels in serum and myocardium were evaluated by enzyme-linked immunosorbent assay (ELISA) at 1, 6, 24 and 48 h after RIPostC. Then, a total of 4 × 106 male MSCs were infused intravenously at 24 h after RIPostC. The number of survived cells in the myocardium was evaluated by real-time polymerase chain reaction analysis for Y chromosome and the heart function was evaluated by echocardiography at 1 month after cell infusion. Furthermore, 10 μg/kg rabbit anti-rat CXCR4 polyclonal antibody was injected intraperitoneally to prove the role of SDF-1α for RIPostC. RIPostC induced an increase in SDF-1α in serum at 1 h and enhanced SDF-1α transcription and protein synthesis in the myocardium at 24 h after the procedure. 1 month after cell transplantation, RIPostC significantly increased MSC myocardial retention by 79.1 ± 12.3% and thereby contributed to enhanced cardiac function in comparison with cell transplantation without RIPostC. Furthermore, blockade with a CXCR4-specific antibody after RIPostC markedly attenuated the enhancement of therapeutic efficacy. We conclude that RIPostC activated SDF-1α expression and enhanced retention of the infused MSCs in the injured myocardium. Priming of the heart with RIPostC might be a novel adjunctive approach for intravenous cell delivery.