Systemic redistribution of the intramyocardially injected mesenchymal stem cells by repeated remote ischaemic...

We investigated the effect of repeated remote ischaemic post-conditioning (RIPoC) on the organ distribution of the intramyocardially injected MSCs in rat myocardial ischemia model. Myocardial ischemia of adult female Sprague-Dawley rats was induced by 30-min. obstruction of the left anterior descending coronary artery. Repeated RIPoC was induced after ischemia with three cycles of 5-min. occlusion and reperfusion of the limb with the frequency of half a day, 1 or 2 days, respectively. Compared with that by single RIPoC, repeated RIPoC transiently reduced oxidative stress, lipid peroxidation and inflammation in ischaemic myocardium; the gene expression of stromal cell-derived factor-1 alpha (SDF-1α) was consistently induced by repeated RIPoC procedures. A total of 4 × 10⁶ male bone marrow-derived MSCs were intramyocardially injected into ischaemic myocardium at 1 week after reperfusion. Three weeks later, immunohistological examination and quantitative reverse transcriptase polymerase chain reaction demonstrated that repeated RIPoC significantly increased MSCs retention in myocardium and decreased MSCs distribution over the lungs, spleen and liver; echocardiography assessment revealed that further cardiac function enhancement imposed by repeated RIPoC procedure. Furthermore, blockade with the anti-CXCR4 antibody before cell transplantation markedly attenuated the benefits of therapeutic efficacy and cardiac function. Repeated RIPoC enhanced MSCs engraftment in ischaemic myocardium and reduced the distribution of MSCs over peripheral organs in a frequency-effect way, but it reached a ceiling of maximal effect when applied with every 1 day. The SDF1α-CXCR4 interaction played a major role in MSCs systemic redistribution induced by repeated RIPoC.