Abstract
Background: Human umbilical cord-derived mesenchymal stem cells (HucMSCs) have been recognized as a promising cell for treating myocardial infarction (MI). Inflammatory response post MI is critical in determining the cardiac function and subsequent adverse left ventricular remodeling. However, the local inflammatory effect of HucMSCs after intramyocardial injection in murine remains unclear. Methods: HucMSCs were cultured and transplanted into the mice after MI surgery. Cardiac function, angiogenesis, fibrosis and hypertrophy, and immune cells infiltration were evaluated between MI-N.S and MI-HucMSC groups. We detected the expression of inflammatory cytokines and their effects on CD4+ T cells migration. Results: HucMSCs treatment can significantly improve the cardiac function and some cells can survive at least 28 days after MI. Intramyocardial administration of HucMSCs also improved angiogenesis and alleviated cardiac fibrosis and hypertrophy. Moreover, we found the much higher numbers of CD4+ T cells and CD4+FoxP3+ regulatory T cells in the heart with HucMSC than that with N.S treatment on day 7 post MI. In addition, the protein level of C-C Motif Chemokine Ligand 5 (CCL5) greatly increased in the HucMSCs treated heart compared to the control. In vitro, HucMSCs inhibited CD4+ T cells migration and addition of CCL5 antibody or C-C Motif Chemokine receptor 5 (CCR5) antagonist significantly reversed this effect. Conclusion: These findings indicated that HucMSCs contributed to cardiac functional recovery and attenuated cardiac remodeling post MI. Intramyocardial injection of HucMSCs upregulated the CD4+FoxP3+ regulatory T cells and contributed to the migration of CD4+ T cells into the injured heart via CCL5/CCR5 pathway.
Human umbilical cord mesenchymal stem cells increase interleukin-9 production of CD4+ T cells