| خلاصه مقاله | Liver fibrosis is associated with the activation of hepatic stellate cells (HSCs) and the upregulation of α-smooth muscle actin (α-SMA) leading to the excessive production and deposition of extra cellular matrix [1, 2]. Aim of this study is to alleviate liver fibrosis by exosome-mediated delivery of obeticholic acid (OCA) to target the activation of HSCs.
Following the isolation and validation of exosomes from Wharton's Jelly mesenchymal stem cells (WJ-MSCs), were loaded with OCA using water bath sonication. The MTT assay was employed to determine the cytotoxicity effects of exosomes (Exo) (30µg), OCA-loaded exosomes (OCA-Exo) (~4µM), and free OCA (10µM) on the HSCs (LX2) cell line. Additionally, considering the significant role of HSCs in liver fibrosis progression, the impact of Exo, free OCA, and OCA-Exo on HSC activity was assessed by quantifying the gene and protein expression of α-SMA using qRT-PCR and western blotting.
According to MTT assay, the findings revealed that none of the treatments significantly influenced cell viability compared to the control group after 48 hours of treatment. The analysis of mRNA and protein expression demonstrated that the delivery of OCA through Exo led to a more substantial decrease in α-SMA expression compared to the Exo or OCA treatment groups.
Based on our study, the combined treatment of Exo-OCA exhibited enhanced effectiveness in targeting HSC activation in hepatic stellate cells compared to exosomes or OCA alone, even at a lower dosage. These results imply a synergistic antifibrotic effect of Exo-OCA in cell culture. |