Bone Marrow Mesenchymal Stem Cells (BMSCs)-Exosomes Carrying MicroRNA-965 Attenuates Allogeneic Renal Transplant Rejection Through Regulation of Janus Kinase/Signal Transducers and Activators of Transcription 3 (JAK/STAT3)

Abstract

This study intends to evaluate the potential effect of BMSC-derived exosomes (exo) on the rejection of allogeneic kidney transplantation in a rat model. BMSCs were cultured and their exos were collected for characterization, in which the expression of miR-965 was detected by PCR. Rats received orthotopic kidney transplantation and treated with exos or PBS followed by analysis of serum creatinine and BUN, inflammatory cell infiltration, renal fibrosis and vascular wall fibrosis by immunohistochemistry staining, JAK2/STAT3 phosphorylation by Western-blot, the inflammatory factor level by ELISA kit, and CD4+ cells differentiation by flow cytometry. miR-965 was enriched in BMSC-derived exo. Treatment with exo ameliorated the allograft rejection, improved renal function, and reduced the histological changes of kidney. In addition, exosomal treatment decreased the level of serum inflammatory cytokines, and altered T cell subpopulations. Meanwhile, fibrosis and neointima formation was reduced as demonstrated by related protein expression and signaling pathways was inactivated in the presence of exos. In conclusion, the miR-965 derived from BMSC-exos mitigated the renal allograft rejection through JAK/STAT3 signaling.