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间充质干细胞条件培养基通过抑制炎症和保护肝血窦内皮细胞来预防辐射诱导的肝损伤。

Mesenchymal stem cell-conditioned medium prevents radiation-induced liver injury by inhibiting inflammation and protecting sinusoidal endothelial cells.

作者信息

Chen Yi-Xing, Zeng Zhao-Chong, Sun Jing, Zeng Hai-Ying, Huang Yan-, Zhang Zhen-Yu

机构信息

Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

出版信息

J Radiat Res. 2015 Jul;56(4):700-8. doi: 10.1093/jrr/rrv026. Epub 2015 Jun 11.

DOI:10.1093/jrr/rrv026
PMID:26070321
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4497399/
Abstract

Current management of radiation-induced liver injury is limited. Sinusoidal endothelial cell (SEC) apoptosis and inflammation are considered to be initiating events in hepatic damage. We hypothesized that mesenchymal stem cells (MSCs) possess anti-apoptotic and anti-inflammatory actions during hepatic irradiation, acting via paracrine mechanisms. This study aims to examine whether MSC-derived bioactive components are protective against radiation-induced liver injury in rats. MSC-conditioned medium (MSC-CM) was generated from rat bone marrow-derived MSCs. The effect of MSC-CM on the viability of irradiated SECs was examined by flow cytometric analysis. Activation of the Akt and ERK pathways was analyzed by western blot. MSC-CM was also delivered to Sprague-Dawley rats immediately before receiving liver irradiation, followed by testing for pathological features, changes in serum hyaluronic acid, ALT, and inflammatory cytokine levels, and liver cell apoptosis. MSC-CM enhanced the viability of irradiated SECs in vitro and induced Akt and ERK phosphorylation in these cells. Infusion of MSC-CM immediately before liver irradiation provided a significant anti-apoptotic effect on SECs and improved the histopathological features of injury in the irradiated liver. MSC-CM also reduced the secretion and expression of inflammatory cytokines and increased the expression of anti-inflammatory cytokines. MSC-derived bioactive components could be a novel therapeutic approach for treating radiation-induced liver injury.

摘要

目前对放射性肝损伤的治疗方法有限。肝血窦内皮细胞(SEC)凋亡和炎症被认为是肝损伤的起始事件。我们假设间充质干细胞(MSC)在肝脏辐射期间具有抗凋亡和抗炎作用,通过旁分泌机制发挥作用。本研究旨在探讨MSC衍生的生物活性成分是否对大鼠放射性肝损伤具有保护作用。MSC条件培养基(MSC-CM)由大鼠骨髓来源的MSC产生。通过流式细胞术分析检测MSC-CM对受辐照SEC活力的影响。通过蛋白质免疫印迹法分析Akt和ERK信号通路的激活情况。在接受肝脏照射前,将MSC-CM立即注入Sprague-Dawley大鼠体内,随后检测病理特征、血清透明质酸、谷丙转氨酶(ALT)和炎性细胞因子水平的变化以及肝细胞凋亡情况。MSC-CM在体外增强了受辐照SEC的活力,并诱导这些细胞中的Akt和ERK磷酸化。在肝脏照射前立即注入MSC-CM对SEC具有显著的抗凋亡作用,并改善了受辐照肝脏的损伤组织病理学特征。MSC-CM还减少了炎性细胞因子的分泌和表达,并增加了抗炎细胞因子的表达。MSC衍生的生物活性成分可能是治疗放射性肝损伤的一种新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e402/4497399/87f6146cd840/rrv02606.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e402/4497399/ac85019e037b/rrv02601.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e402/4497399/df5480a6ba9b/rrv02602.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e402/4497399/87f6146cd840/rrv02606.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e402/4497399/ac85019e037b/rrv02601.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e402/4497399/df5480a6ba9b/rrv02602.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e402/4497399/4905a70c453f/rrv02603.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e402/4497399/c00878ff47b4/rrv02604.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e402/4497399/15c3a9a531c8/rrv02605.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e402/4497399/87f6146cd840/rrv02606.jpg

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Hepatocyte growth factor gene-modified mesenchymal stem cells reduce radiation-induced lung injury.
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