Transplantation of bone marrow cells reduces CCl 4-induced liver fibrosis in mice

Kyung Ah Cho, Goh Woon Lim, Sun Young Joo, So Youn Woo, Ju Young Seoh, Su Jin Cho, Ho Seong Han, Kyung Ha Ryu

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46 Scopus citations

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. Conclusion: 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.

Original languageEnglish
Pages (from-to)932-939
Number of pages8
JournalLiver International
Volume31
Issue number7
DOIs
StatePublished - Aug 2011

Keywords

  • Bone marrow cells
  • CCl
  • G-CSF
  • Liver fibrosis

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