Repeated versus single transplantation of mesenchymal stem cells in carbon tetrachloride-induced liver injury in mice

Cell Biol Int. 2013 Apr;37(4):340-7. doi: 10.1002/cbin.10048.


Despite its numerous limitations, liver transplants are the only definite cure for end-stage liver disease. Various stem cell populations may contribute to liver regeneration, of which there is accumulating evidence of the contribution of mesenchymal stem cells (MSCs). This study examines the hypothesis that repeated infusions of human bone marrow-derived MSCs (hBMMSCs)can improve liver injury in an experimental model. MSCs were intravenously transplanted into immunosuppressed mice with carbon tetrachloride (CCl(4))-induced liver fibrosis. Transplanting 3x10(6) MSCs in three divided doses improved survival,liver fibrosis and necrosis compared with injection of the same number of MSCs in a single dose. This was accompanied by increased influence on the expression of the fibrogenic/fibrolytic related genes Col1a1, Timp1 and Mmp13 in the repeated transplant group. Repeat administration of MSCs was three times more effective in homing of PKH-tagged transplanted cells 3 weeks post-transplant compared with the single transplant group. The benefits of repeated transplants may be of considerable significance in clinical trials on liver failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Tetrachloride
  • Cells, Cultured
  • Chemical and Drug Induced Liver Injury / therapy*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Gene Expression
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / therapy*
  • Liver Regeneration
  • Mesenchymal Stem Cell Transplantation*
  • Mice


  • Extracellular Matrix Proteins
  • Carbon Tetrachloride