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Intra-portal transplantation of bone marrow stromal cells ameliorates liver fibrosis in mice |
Jin-Fang Zheng and Li-Jian Liang |
Guangzhou, China
Author Affiliations: Department of Hepatobiliary Surgery, People's Hospital of Hainan Province, Haikou 570311, China (Zheng JF); Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China (Liang LJ)
Corresponding Author: Jin-Fang Zheng, MD, Department of Hepatobiliary Surgery, People's Hospital of Hainan Province, Haikou 570311, China (Tel: 86-898-68642216; Email: Zhengjf2000@hotmail.com) |
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Abstract BACKGROUND: Bone marrow cells can differentiate into hepatocytes in a suitable microenvironment. This study was undertaken to investigate the effects of transplanted bone marrow stromal cells (BMSCs) on liver fibrosis in mice.
METHODS: BMSCs were harvested and cultured from male BALB/c mice, then transplanted into female syngenic BALB/c mice via the portal vein. After partial hepatectomy, diethylnitrosamine (DEN) was administered to induce liver fibrosis. Controls received BMSCs and non-supplemented drinking water, the model group received DEN with their water, and the experimental group received BMSCs and DEN. Mice were killed after 3 months, and ALT, AST, hyaluronic acid (HA), and laminin (LN) in serum and hydroxyproline (Hyp) in the liver were assessed. Alpha-smooth muscle actin (α-SMA) in the liver was assessed by immunohistochemistry. Bone marrow-derived hepatocytes were identified by fluorescent in situ hybridization (FISH) in liver sections.
RESULTS: BMSCs were shown to differentiate into hepatocyte-like phenotypes after hepatocyte growth factor treatment in vitro. Serum ALT, AST, HA, and LN were markedly reduced by transplanted BMSCs. Liver Hyp content and α-SMA staining in mice receiving BMSCs were lower than in the model group, consistent with altered liver pathology. FISH analysis revealed the presence of donor-derived hepatocytes in the injured liver after cross-gender mouse BMSC transplantation. After three months, about 10% of cells in the injured liver were bone marrow-derived.
CONCLUSION: BMSCs transplanted via the portal vein can convert into hepatocytes to repair liver injury induced by DEN, restore liver function, and reduce liver fibrosis.
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