Exosomes from Placenta-Derived Mesenchymal Stem Cells Are Involved in Liver Regeneration in Hepatic Failure Induced by Bile Duct Ligation.
Exosomes from Placenta-Derived Mesenchymal Stem Cells Are Involved in Liver Regeneration in Hepatic Failure Induced by Bile Duct Ligation.
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DOI：
10.1155/2020/5485738
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发表时间：
2020
影响因子：
4.3
通讯作者：
Kim GJ
中科院分区：
文献类型：
--
作者：
Jun JH;Kim JY;Choi JH;Lim JY;Kim K;Kim GJ
虽然肝脏具有再生能力，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-MSCs）具有独特的特征，如出生后胎盘废物的回收，易于获得，丰富的细胞数量和强大的免疫抑制特性。以前，我们报道了PD-MSCs可以通过抗纤维化和自噬机制再生肝衰竭的肝脏。许多报告已经调查了由泡体出芽形成并从干细胞发射到血液中的外泌体是否在各种疾病中具有治疗潜力。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肝衰竭大鼠模型（胆管结扎，BDL）的外泌体中CRP的表达，并通过CRP与PD-MSC移植后血管生成之间的相关性来评估治疗效果。通过LC-MS分析和沉淀溶液分析移植PD-MSC的BDL大鼠模型中的外泌体。在体内和体外通过实时PCR、Western印迹和免疫荧光（IF）对外来体、CRP和与这些分子相关的因子进行了评价和定量。CRP存在于来自大鼠模型血清的外来体中，并且通过PD-MSC移植而增加。在外泌体中，CRP上调与BDL大鼠肝移植PD-MSCs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调节大鼠肝细胞中的Wnt通路和血管形成。因此，我们的研究结果表明，CRP在外泌体分泌的PD-MSC功能通过Wnt信号通路的血管生成。
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.
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影响因子：
25.7
作者：
Nojima H;Freeman CM;Schuster RM;Japtok L;Kleuser B;Edwards MJ;Gulbins E;Lentsch AB
通讯作者：
Lentsch AB
影响因子：
3.8
作者：
Morris, Andrew D.;Dalal, Sidd;Brewster, Luke P.
通讯作者：
Brewster, Luke P.
影响因子：
5.5
作者：
Molins, Blanca;Anna Pascual, Mendez;Martorell, Jordi
通讯作者：
Martorell, Jordi
影响因子：
2.9
作者：
Lee, Hyun-Jung;Jung, Jieun;Kim, Gi Jin
通讯作者：
Kim, Gi Jin
影响因子：
6.1
作者：
Peyvandi AA;Roozbahany NA;Peyvandi H;Abbaszadeh HA;Majdinasab N;Faridan M;Niknazar S
通讯作者：
Niknazar S