Activation of Invariant Natural Killer T Cells Further Ameliorates Post-Infarct Cardiac Remodeling in Mice With MSC Transplantation

Abstract Background：The purpose of this study was to examine the effect of MSCs on the infiltration of iNKT cells and further observe whether the activation of iNKT cells could assist the therapeutic action of MSCs on ventricular remodeling.Methods：Mice with MI were sacrificed at day 7, 14, 28 and hearts were excised. qRT-PCR for Vα14Jα18 (a special marker of iNKT cell for C57BL/6) was carried out. 25μL serum-free medium(Me)、complete medium with 1×106 MSCs or without MSCs were respectively injected into myocardium in five points. After 7, 14, 28 days, qRT-PCR for Vα14Jα18 was respectively preformed. Gene expressions of Vα14Jα18 in PLV with the injection of cMe alone and cMe with PGE2, L-NMMA, indomethacin, anti-TGF at day 7 were also analyzed. Then, the experiment was performed in five groups: MI+Me, MI+MSCs, MI+MSCs+indome, MI+α-GC and MI+MSCs+ α-GC. After 28 days, heart tissue fibrosis was accessed by Masson trichrome dyeing and apoptosis was evaluated by TUNEL staining and western blotting for caspase-3 protein.Results：The iNKT cells infiltrating into the PLV was significantly increased at day 7 after MI (1.72-fold changes from baseline, P<0.05), but almost returned to baseline level at day 14 and 28. Compared to MI+Me group(1.76±0.20-fold), iNKT cells infiltration was significantly suppressed at day 7 in MI+MSCs (1.25±0.29-fold, P<0.05) and MI+cMe groups (1.19±0.25-fold, P<0.05). In MI+cMe+indome and MI+cMe+PGE2 group, the changes of iNKT cells infiltration were respectively 1.74- and 1.04-fold (vs 1.20-fold in MI+cMe group, P<0.05). Combined MSCs transplantation with iNKT cells activation, myocyte apoptosis and interstitial fibrosis in PLV were both significantly attenuated. Conclusions:In the infarcted mouse model, MSCs suppressed the infiltration of iNKT cells by secreting PGE2. Activating iNKT cells could assist the therapeutic effect of MSCs on ventricular remodeling, with attenuated apoptosis and interstitial fibrosis.