Transplantation of human matrix metalloproteinase-1 gene-modified bone marrow-derived mesenchymal stem cell attenuates CCL4-induced liver fibrosis in rats

被引：35

作者：

Du, Chao ^{[1
]}

Jiang, Mingde ^{[1
]}

Wei, Xiaolong ^{[1
]}

Qin, Jianpin ^{[1
]}

Xu, Hui ^{[1
]}

Wang, Yunxia ^{[1
]}

Zhang, Yong ^{[1
]}

Zhou, Dejiang ^{[1
]}

Xue, Hongli ^{[1
]}

Zheng, Shumei ^{[1
]}

Zeng, Weizheng ^{[1
]}

机构：

[1] Chengdu Mil Gen Hosp, Dept Gastroenterol & Hepatol, 270 Rongdu Rd, Chengdu 610083, Sichuan, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE | 2018年 / 41卷 / 06期

基金：

中国国家自然科学基金;

关键词：

bone marrow-derived mesenchymal stem cells; matrix metalloproteinase 1; liver fibrosis; stem cell transplantation; rats; HEPATIC-FIBROSIS; STROMAL CELLS; DIFFERENTIATION; MIGRATION; EXPRESSION; HEPATOCYTE; MECHANISMS; CIRRHOSIS; DELIVERY; THERAPY;

D O I：

10.3892/ijmm.2018.3516

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

It has been reported that bone marrow-derived mesenchymal stem cells (BMSCs) alleviated liver fibrosis. We investigated whether BMSCs transfected with human matrix metalloproteinase 1 (BMSCs/MMP1) would improve their therapeutic effect in liver fibrosis induced by carbon tetrachloride (CCl4) in rats. BMSCs were transfected with an adenovirus carrying enhanced green fluorescence protein (GFP) and human MMP1 gene. BMSCs or BMSCs/MMP1 were directly injected into fibrotic rats via the tail vein. GFP-labeled cells appeared in the fibrotic liver after BMSC transplantation. The expression of BMSCs/MMP1 elevated levels of MMP1 in vitro. Although BMSC administration reduced liver fibrosis, transplantation of BMSCs/MMP1 enhanced the reduction of liver fibrosis to a higher level. Treatment with BMSCs/MMP1 not only decreased collagen content but also suppressed activation of hepatic stellate cells (HSCs) in fibrotic liver, which led to subsequent improvement of both liver injury and fibrosis. Treatment with BMSCs/MMP1 resulted in an improved therapeutic effect compared with BMSCs alone, which is probably because of the sustainably expressed MMP1 level in the liver. BMSCs/MMP1 transplantation not only improved biochemical parameters but also attenuated progression of liver fibrosis, suggesting that BMSCs may be a potential cell source in preventing liver fibrosis and MMP1 gene may enhance the anti-fibrotic effect of BMSCs.

引用

页码：3175 / 3184

页数：10

共 56 条

[1]

Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers [J].