Mesenchymal stem cell infusion therapy in a carbon tetrachloride-induced liver fibrosis model affects matrix metalloproteinase expression.
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.
Rabani
Vahideh
V
Department of Stem Cells and Developmental Biology, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Shahsavani
Mansoureh
M
Gharavi
Marzieh
M
Piryaei
Abbas
A
Azhdari
Zahra
Z
Baharvand
Hossein
H
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002251:Carbon Tetrachloride; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000201:enzymology / Q000628:therapy*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D000199:Actins; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D002251:Carbon Tetrachloride; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9