Abstract: Abstract  Objective   We aimed at SDF-1α /CXCR4 signal pathway on hypoxic preconditioning endothelial progenitor cells(HEPCs), investigating the therapeutic effectiveness of transplantation HEPCs into acute infarcted myocardium Method    Bone marrow endothelial progenitor cells(EPCs) were islolated from syngeneic adult male Wistar rats, normoxic culture on EPCs for 4 days and 1%O2+5%CO2+94%N2 culture for 3 days. Using Boyden Chamber assay to compare migration ability between EPCs and HEPCs towards 100ng/ml bone marrow derived factor -1α(SDF-1α). Using western blot assay to detect expression of CXCR4, which is the solo receptor of SDF-1αon cells surface. Then, 26 syngeneic adult male Wistar rats were randomized into 3 groups: Control(n=8)，EPCs(n=9) and HEPCs(n=9),set up acute myocardium infarction animal model. At infarction, the rats received 5-points peri-infarct intramyocardial injections of PBS 200ul, 2×106 EPCs and 2×106 HEPCs. After 4 weeks, using ECHO to analyze improvement of cardiac function by haemodynamics parameters. Result    Compare with EPCs, the migration ability of HEPCs towards 100ng/ml SDF-1α was increased significant(549±78 cells/HPF vs 118±22 cells/HPF, p=0.009). The result of western blot of CXCR4 revealed that hypoxic preconditioning on EPCs upregulated CXCR4 expression on cell surface. After 4 weeks of transplantation, echocardiography of rats showed that compare HEPCs with EPCs and Control，systolic left ventricular internal diameter(LVIDs), ejection fraction(EF%) improved significantly. Compare HEPCs and EPCs with Control, diastolic left ventricular internal diameter(LVIDd) improved significantly, but there is no difference of LVIDd between HEPCs and EPCs. Conclusion    Regulating SDF-1α/CXCR4 pathway increased treatment effectiveness of cell transplantation and optimized therapeutic strategy on ischemia heart disease. Hypoxic preconditioning of EPCs upregulate CXCR4 expression on cell surface, improve migration ability of EPCs towards SDF-1α through SDF-1α/CXCR4 signal pathway. Transplantation of HEPCs after acute myocardium infarction limited left ventricular remodeling, improved cardiac function entirely.

Key words: receptors, CXCR4, Stem cell transplantation, endothelial cells, bone marrow cells, acute myocardiac infarction, anoxia, 趋化因子 CXCL12