Human Adipose-derived mesenchymal stem cells promote lymphocyte apoptosis and alleviate atherosclerosis via miR-125b-1-3p/BCL11B signal axis.

BACKGROUND: Mesenchymal stem cells (MSCs) have shown great potential in the treatment of cardiovascular diseases, with fat being a more accessible source of MSCs. This study investigated the effect of human adipose-derived mesenchymal stem cells (hMSCs-Ad) exosomes on T lymphocytes and its role in atherosclerosis (AS).

METHODS: The exosomes were preliminarily isolated hMSCs-Ad and co-cultured with human H9 T lymphocytes. The effects of hMSCs-Ad exosomes on the proliferation and apoptosis of H9 were examined by performing functional experiments. The serum lipid level and inflammatory factor level in tail vein of mice were measured by biochemical analyzer and enzyme linked immunosorbent assay (ELISA) respectively.

RESULTS: The hMSCs-Ad-derived exosomes up-regulate the expression of micro (mi)R-125b-1-3p in H9 and AS arterial tissues. miR-125b-1-3p shared a targeted binding site with B-cell chronic lymphocytic leukemia (CLL)/lymphoma 11B gene (BCL11B). miR-125b-1-3p negatively regulated the expression of BCL11B in H9, and that knocking down BCL11B in H9 promoted its apoptosis. Injection of hMSCs-Ad-derived exosomes via the tail vein effectively reduced blood lipid and inflammatory factors, and that relieved the symptoms of AS in AS model mice.

CONCLUSIONS: miR-125b-1-3p was expressed in hMSCs-Ad exosomes and can promote T lymphocyte apoptosis and alleviate AS by down-regulating BCL11B expression. It provides potential molecular targets for the clinical treatment of AS.