Mesenchymal stem cells restore CCl4-induced liver injury by an antioxidative process

被引:84
作者
Cho, Kyung-Ah [3 ]
Woo, So-Youn [3 ]
Seoh, Ju-Young [3 ]
Han, Ho-Seong [2 ]
Ryu, Kyung-Ha [1 ]
机构
[1] Ewha Womans Univ, Sch Med, Ewha Med Res Ctr, Dept Pediat, Seoul, South Korea
[2] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea
[3] Ewha Womans Univ, Sch Med, Ewha Med Res Ctr, Dept Microbiol, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
bone marrow; liver injury; mesenchymal stem cell; oxidative stress; UMBILICAL-CORD BLOOD; OXIDATIVE STRESS; STROMAL CELLS; REGENERATION; MICE;
D O I
10.1042/CBI20110634
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have investigated BM (bone marrow)-derived MSCs (mesenchymal stem cells) for the treatment of liver injury. It was hypothesized that MSC-mediated resolution of liver injury could occur through an antioxidative process. After being injected with CCl4 (carbon tetrachloride), mice were injected with syngenic BM-derived MSCs or normal saline. Oxidative stress activity of the MSCs was determined by the analysis of ROS (reactive oxygen species) and SOD (superoxide dismutase) activity. In addition, cytoprotective genes of the liver tissue were assessed by real-time PCR and ARE (antioxidant-response element) reporter assay. Up-regulated ROS of CCl4-treated liver cells was attenuated by co-culturing with MSCs. Suppression of SOD by adding an SOD inhibitor decreased the effect of MSCs on injured liver cells. MSCs significantly increased SOD activity and inhibited ROS production in the injured liver. The gene expression levels of Hmox-1 (haem oxygenase-1), BI-1 (Bax inhibitor-1), HGF (hepatocyte growth factor), GST (glutathione transferase) and Nrf2 (nuclear factor-erythoid 2 p45 subunit-related factor 20), attenuated by CCl4, were increased up to basal levels after MSC transplantation. In addition, MSCs induced an ARE, shown by luciferase activity, which represented a cytoprotective response in the injured liver. Evidence of a new cytoprotective effect is shown in which MSCs promote an antioxidant response and supports the potential of using MSC transplantation as an effective treatment modality for liver disease.
引用
收藏
页码:1267 / 1274
页数:8
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