Intra-portal transplantation of bone marrow stromal cells ameliorates liver fibrosis in mice.
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 (alpha-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 alpha-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.


CONCLUSIONS
BMSCs transplanted via the portal vein can convert into hepatocytes to repair liver injury induced by DEN, restore liver function, and reduce liver fibrosis.
Zheng
Jin-Fang
JF
Department of Hepatobiliary Surgery, People's Hospital Hainan Provice, Haikou, China. Zhengjf2000@hotmail.com
Liang
Li-Jian
LJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects; D022781:Hepatocytes / Q000473:pathology; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007275:Injections, Intravenous; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011169:Portal Vein; D017154:Stromal Cells / Q000637:transplantation*