Exosomes from Placenta-Derived Mesenchymal Stem Cells Are Involved in Liver Regeneration in Hepatic Failure Induced by Bile Duct Ligation.

Abstract

Although the liver has a regenerative capacity, hepatic failure is a severe and irreversible chronic disease. Placenta-derived mesenchymal stem cells (PD-MSCs) have distinctive features, such as recycling of the placenta waste after birth, ease of accessibility, abundant cell numbers, and strong immunosuppressive properties. Previously, we reported that PD-MSCs can regenerate the liver in hepatic failure through antifibrotic and autophagic mechanisms. Many reports have investigated whether exosomes, which are formed by the budding of vesicular bodies and are emitted into the blood, from stem cells have therapeutic potential in various diseases. C-reactive protein (CRP) is produced in hepatocytes and secreted via vessels. Therefore, the objectives of this study were to compare the expression of CRP in exosomes of a hepatic failure rat model (bile duct ligation, BDL) and to evaluate the therapeutic effect by their correlation between CRP and angiogenesis depending on PD-MSC transplantation. The exosomes were analyzed in a BDL rat model with transplantation of PD-MSCs through LC-MS analysis and precipitation solution. The exosomes, CRP, and factors related to these molecules were evaluated and quantified in exosomes as well as investigated by real-time PCR, Western blot, and immunofluorescence (IF) in vivo and in vitro. CRP was present in exosomes from serum of a rat model and increased by PD-MSC transplantation. In the exosomes, CRP upregulated the factors related to the Wnt signaling pathway and angiogenesis in the BDL rat liver-transplanted PD-MSCs. Also, CRP regulated the Wnt pathway and vascularization in rat hepatocytes by interacting with endothelial cells. Therefore, our findings indicate that CRP in exosomes excreted by PD-MSCs functions in angiogenesis via the Wnt signaling pathway.