Mesenchymal stem cell infusion therapy in a carbon tetrachloride-induced liver fibrosis model affects matrix metalloproteinase expression

Cell Biol Int. 2010 Apr 27;34(6):601-5. doi: 10.1042/CBI20090386.

Abstract

In order to investigate the effects of bone marrow-derived MSCs (mesenchymal stem cells) in reversing liver fibrosis and to determine their possible mechanism of action, mouse MSCs were infused into the tail vein of a CCl(4) injection mouse chronic model. MSCs caused a decrease in liver fibrosis histopathologically, 4 weeks after transplantation. The reduction in liver collagen was confirmed by quantitative analysis. Moreover, lipid peroxidation in the CCl(4)/MSC group decreased significantly. Quantitative RT (reverse transcription)-PCR analysis showed administration of MSCs has a significant antifibrotic effect as evidenced by the decrease in expression of liver collagen and increase in MMP13 (matrix metalloproteinase 13) in the CCl(4)/MSC group when compared with the CCl(4) group, 4 weeks after transplantation. The expression of alphaSMA (smooth muscle actin) and TIMP1 was also down-regulated in the CCl(4)/MSC group. Additionally, the expression of MMP9 was significantly up-regulated in the CCl(4)-treated group; however, there was no significant change after MSC injection. Few engrafted cells in the recipient liver and were able to differentiate into albumin-positive cells. In conclusion, MSCs can enhance recovery of a CCl(4)-injured mouse liver through their influence in reducing collagen deposition by possibly affecting expression of MMPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Bone Marrow Cells / cytology
  • Carbon Tetrachloride
  • Collagen / genetics
  • Collagen / metabolism
  • Disease Models, Animal
  • Down-Regulation
  • Female
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / enzymology
  • Liver Cirrhosis / therapy*
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Mice
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Up-Regulation

Substances

  • Actins
  • Tissue Inhibitor of Metalloproteinase-1
  • Collagen
  • Carbon Tetrachloride
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 9