Bone Marrow Mesenchymal Stem Cell-derived Exosomes Exert Therapeutic Effects by Attenuating Fibrosis and Facilitating Hepatocyte Proliferation via the Anti-pyroptosis Pathway in a Rat Cirrhosis Model

Abstract BackgroundLiver cirrhosis, which lacks a specific therapy, induces a substantial economic burden and affects quality of life. Exosomes are nanosized vesicles that are secreted by cells transfer bioactive molecules to regulate metastasis and have attracted immense interest as a therapeutic option for liver cirrhosis. Therefore, in this study, we explored the efficacy and dose of exosomes derived from rat bone marrow mesenchymal stem cells (Exos-rBMMSC) in a hepatic cirrhosis rat model. ResultsFour weeks after exosome therapy, NLRP3, GSDMD, cleaved caspase-1, IL-1β and IL-18 expression levels in the 200 μg and 400 μg Exos-rBMMSC groups were significantly decreased compared to those in the liver cirrhosis group (P<0.05). Similar results were observed in the hepatic function assay; serum levels of aspartate aminotransferase and alanine aminotransferase were decreased, and albumin was increased. The histopathology results showed that 200 μg and 400 μg of Exos-rBMMSC significantly relieved collagen deposition, while 100 μg of Exos-rBMMSC induced no marked improvements compared to those in the liver cirrhosis group. The localization of PKH67-labelled Exos-rBMMSC was verified microscopically, and these particles coexpressed PCNA, NLRP3, GSDMD and Caspase-1. ConclusionsOur findings suggest that Exos-rBMMSC accelerate hepatocyte proliferation and relieve liver fibrosis, which may be a promising therapeutic strategy for liver cirrhosis.