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 CCl4 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 CCl4/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 CCl4/MSC group when compared with the CCl4 group, 4 weeks after transplantation. The
expression of aSMA (smooth muscle actin) and TIMP1 was also down-regulated in the CCl4/MSC group. Additionally,
the expression of MMP9 was significantly up-regulated in the CCl4-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 CCl4-injured mouse liver through their influence in reducing collagen
deposition by possibly affecting expression of MMPs.
