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Background To study the efficacy of intravenous MSCs transplantation under diagnostic ultrasound (US) irradiated SDF-1-loaded Microbubbles (MBs) on the improvement of MSCs homing and cardiac function after rat myocardial infarction.Methods Covalent binding method was used to prepare SDF-1-loaded MBs.MSCs were cultured in hypoxic environment(1% O2, 94% N2,5% CO2) for 24h.FCM was used to detect the surface CXCR4 on MSCs.Transwell migration assay was performed to evaluate the migration ability of MSCs.Hypoxic preconditioned rat MSCs were used in cell transplantation.The number of GFP-positive cells within ischemic myocardium in the four groups was counted.After 7d implantation of unlabeled MSCs, IHC was used to detect the expression of hepatocyte growth factor (HGF).Western Blot to analyze SDF-1 and VEGF.HE staining to detect the capillary density (CD), and echocardiography to evaluate the systolic function of left ventricular (LV).Results SDF-1 loaded microbubbles were successfully prepared.After hypoxic precondition,the proportion of MSCs expressed membrane CXCR4 was increased from (0.86±0.21) % to (8.52±2.17) %, and to (15.62±3.65) % after UTMD treatment.The number of successfully migrated cells in MSC+UMSDF-1 group (184.57±19.52) was significantly more than that of the MSC+UM group (95.25±9.21) and of the control group (43.13±6.86),and sharply reduced to (62.34±8.95) after AMD3100 pre-treatment, all P<0.01.The number of GFP-positive MSCs (58.33 ±13.51) in MSC + UMSDF-1 group was 1.27-fold higher than of MSC+UM group (45.92±8.08) and 2.12-flod greater than MSC group (27.46±5.21).The CD in the MSC+UMSDF-1 group was much greater than that of the other three groups.SDF-1 and VEGF level reach the highest in the MSC+UMSDF-1 group,followed by the MSC+UM,the MSC,and the control group.Significant differences of LVEF were indicated between the MSC+UMSDF-1 group [(67.83±5.78)%] and the MSC+UM group [(58.83±5.50)%], the MSC group [(48.74±3.13)%] and the control group [(39.80±4.51)%], all P<0.01.Conclusion The homing and repairing capability of MSCs in post-MI rats were successfully improved after hypoxic preconditioning MSCs implantation mediated by ultrasound-targeted SDF-1-loaded microbubbles destruction.