Open Access

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

  • Authors:
    • Chao Du
    • Mingde Jiang
    • Xiaolong Wei
    • Jianpin Qin
    • Hui Xu
    • Yunxia Wang
    • Yong Zhang
    • Dejiang Zhou
    • Hongli Xue
    • Shumei Zheng
    • Weizheng Zeng
  • View Affiliations

  • Published online on: February 27, 2018     https://doi.org/10.3892/ijmm.2018.3516
  • Pages: 3175-3184
  • Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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June-2018
Volume 41 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Du C, Jiang M, Wei X, Qin J, Xu H, Wang Y, Zhang Y, Zhou D, Xue H, Zheng S, Zheng S, et al: Transplantation of human matrix metalloproteinase-1 gene-modified bone marrow-derived mesenchymal stem cell attenuates CCL4-induced liver fibrosis in rats. Int J Mol Med 41: 3175-3184, 2018
APA
Du, C., Jiang, M., Wei, X., Qin, J., Xu, H., Wang, Y. ... Zeng, W. (2018). Transplantation of human matrix metalloproteinase-1 gene-modified bone marrow-derived mesenchymal stem cell attenuates CCL4-induced liver fibrosis in rats. International Journal of Molecular Medicine, 41, 3175-3184. https://doi.org/10.3892/ijmm.2018.3516
MLA
Du, C., Jiang, M., Wei, X., Qin, J., Xu, H., Wang, Y., Zhang, Y., Zhou, D., Xue, H., Zheng, S., Zeng, W."Transplantation of human matrix metalloproteinase-1 gene-modified bone marrow-derived mesenchymal stem cell attenuates CCL4-induced liver fibrosis in rats". International Journal of Molecular Medicine 41.6 (2018): 3175-3184.
Chicago
Du, C., Jiang, M., Wei, X., Qin, J., Xu, H., Wang, Y., Zhang, Y., Zhou, D., Xue, H., Zheng, S., Zeng, W."Transplantation of human matrix metalloproteinase-1 gene-modified bone marrow-derived mesenchymal stem cell attenuates CCL4-induced liver fibrosis in rats". International Journal of Molecular Medicine 41, no. 6 (2018): 3175-3184. https://doi.org/10.3892/ijmm.2018.3516