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.

中文翻译：

---

胎盘来源间充质干细胞的外来体参与胆管结扎引起的肝衰竭的肝再生。

尽管肝脏具有再生能力，但肝功能衰竭是一种严重且不可逆的慢性疾病。胎盘来源的间充质干细胞（PD-MSC）具有鲜明的特征，例如出生后胎盘废物的回收，易于获得，细胞数量丰富以及强大的免疫抑制特性。以前，我们报道过PD-MSCs可通过抗纤维化和自噬机制在肝衰竭中再生肝脏。许多报告调查了由水泡体萌芽形成的外泌体，并从干细胞释放到血液中，这些外泌体在各种疾病中是否具有治疗潜力。C反应蛋白（CRP）在肝细胞中产生并通过血管分泌。因此，本研究的目的是比较CRP在肝衰竭大鼠模型（胆管结扎，BDL）的外泌体中的表达，并通过CRP与依赖PD-MSC移植的血管生成之间的相关性来评估治疗效果。通过LC-MS分析和沉淀溶液，在PD-MSCs移植的BDL大鼠模型中分析了外泌体。外泌体，CRP和与这些分子相关的因子在外泌体中进行了评估和定量，并通过实时PCR，蛋白质印迹和免疫荧光（IF）进行了研究体内和体外。CRP存在于大鼠模型的外来体中，并因PD-MSC移植而增加。在外泌体中，CRP上调了BDL大鼠肝移植PD-MSC中Wnt信号通路和血管生成相关的因子。此外，CRP通过与内皮细胞相互作用来调节大鼠肝细胞中的Wnt途径和血管形成。因此，我们的发现表明，PD-MSCs分泌的外泌体中的CRP通过Wnt信号通路在血管生成中起作用。