Exosomal circ-RBM23 sponging miR-139-5p to promote liver regeneration through RRM2/AKT/mTOR pathway

Background: Exosomes are small nano-size membrane vesicles and are involved in intercellular interaction. Here, we examined if exosomes obtained from human placental stem cells promote liver regeneration after partial hepatectomy. Methods Exosomes generated from primary human placental-derived mesenchymal stem cells (hPMSCs) were isolated and characterized. Cell co-culture model was used to clarify whether exosomes can induce hepatocyte proliferation in vitro . Partial hepatectomy mouse model was used to evaluate whether exosomes can promote hepatocytes proliferation in vivo . Results Our results demonstrated that human placental-derived stem cells exosomes (hPMSCs-exo) can induce hepatocyte proliferation in vitro and in vivo . Mechanistically, exosomal circ-RBM23 served as a ceRNA (competing endogenous RNAs) for miR-139-5p, regulated RRM2 and accelerated proliferation through AKT/mTOR pathways. Ablation of circ-RBM23 suppressed the pro-proliferative effect of exosomes. Conclusions The hPMSCs exosomal circ-RBM23 stimulated cell proliferation and liver regeneration after 70% partial hepatectomy by a ceRNA network mechanism. Our findings highlight a potential novel therapeutic avenue for liver regeneration.