The Effect Of Stromal Cell-derived Factor 1 On Mesenchymal Stem Cells Homing To Myocardial Infarct Site

Mesenchymal stem cells; Homing; Myocardial infarction;Cardiac function; Stromal cell-derived factor 1[Objective] To investigate the expression of SDF-1 in and aroundmyocardial infarct site, and the effect of SDF-1 on MSCs homing tomyocardial infarct site.[Methods] Myocardial infarction was induced in inbred Fischer 344 ratsby left anterior descending artery ligation. Coronary artery (LAD) wasligated by 6-0 prolene thread. All the rats were devided into two groups:SDF-1 detection group and AMI group. SDF-1 detection group: SDF-1expression were measured by in situ hybridization andimmunohistochemistry in sham operated or infarcted hearts at 1, 2, 4, 7,14, 28 and 56 days post MI. AMI group: MSCs from donor rats werelabeled with BrdU. SDF-1, anti-SDF-1 antibody or saline was injectedinto peri-infarct myocardium 4 days after MI. Then, a total of 5×10~6 cellsin 2.5 mL of PBS or equal volume PBS alone were injected through thetail vein. The number of the labeled MSCs in the infarcted hearts was counted 3 days post injection. Cardiac function and blood vessel densitywere assessed 28 days post injection.[Results] SDF-1 detection group: SDF-1 expression increased andpeaked at the first day and decreased thereafter post MI in the center ofmyocardial infarct site and peri-myocardial infarct site. However, SDF-1remained unchanged away from myocardial site and in sham operatedhearts. AMI group: The MSCs enrichment in the host hearts were moreabundant in the MI sub-groups than that in the non-MI sub-group(P=0.000), SDF-1 injected sub-group than anti-SDF-1 antibody andsaline injected sub-groups (P=0.000). Cardiac function was improvedmore in SDF-1 injected sub-group than anti-SDF-1 antibody and salineinjected sub-groups (P=0.000). Neovascularization in SDF-1 injectedsub-group significantly increased than that of other sub-groups(P=0.000).[Conclusions] Myocardial SDF-1 expression increased only in the earlyphase post MI. SDF-1 may enhance MSCs homing to injured heart andimprove cardiac function by promoting neovascularization. In order toimprove the effect of therapy by using SDF-1, a suitable time courseshould be choosed, except that expression of SDF-1 should bereestablished.