title: Transplantation of bone marrow cells reduces CCl4 -induced liver fibrosis in mice.
abstract: BACKGROUND
  We investigated the reversibility of liver fibrosis induced with a CCl(4) injection and the role of stem cells in reversing the hepatic injury. Furthermore, the most effective cell fraction among bone marrow cells (BMCs) in the repair process was analysed.
  
  
  METHODS
  C57BL/6 mice were divided into four groups after 5 weeks of injection of CCl(4) : control, sacrificed after 5 weeks, sacrificed at 10 weeks and sacrificed 5 weeks later after GFP-donor BM transplantation. Liver function tests and real-time polymerase chain reaction (PCR) of markers indicating liver fibrosis were compared between the groups. To identify the most effective BMC fraction that repairs liver injury, the mice were divided into three groups after the injection of CCl(4) for 2 days: granulocyte colony stimulating factor (G-CSF) only, mononuclear cell (MNC) transplantation and Lin-Sca-1+c-kit+haematopoietic stem cell (HSC) transplantation. Eight days after transplantation, the mice were harvested and morphometric, immunohistochemical analyses were performed to compare the expression of extracellular matrix and liver fibrosis-related factors.
  
  
  RESULTS
  The liver fibrosis induced by CCl(4) was not spontaneously recovered but was persistent until 10 weeks, but the group injected with BMCs had less fibrosis and better liver function. Mobilization with G-CSF increased the recovery of the injured liver and the best results were seen in those mice administered the MNC fraction and Lin-Sca-1+c-kit+HSC fraction, with no difference between the two groups.
  
  
  CONCLUSIONS
  BMC transplantation and stem cell mobilization with G-CSF effectively treats liver injury in mice. These are promising techniques for autologous transplantation in humans with liver fibrosis.
authors.affiliation: Department of Microbiology, School of Medicine, Ewha Womans University, Seoul, Korea.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Cho
authors.forename: Goh-Woon
authors.initials: GW
authors.lastname: Lim
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Joo
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Woo
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Seoh
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Cho
authors.forename: Ho-Seong
authors.initials: HS
authors.lastname: Han
authors.forename: Kyung-Ha
authors.initials: KH
authors.lastname: Ryu
mesh_terms: D000818:Animals; D017209:Apoptosis; D016026:Bone Marrow Transplantation / Q000379:methods*; D054407:Chemokine CCL4 / Q000633:toxicity; D017931:DNA Primers / Q000235:genetics; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006652:Histological Techniques; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000637:transplantation; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000628:therapy*; D008111:Liver Function Tests; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction
chemical_list: D054407:Chemokine CCL4; D017931:DNA Primers; D016179:Granulocyte Colony-Stimulating Factor