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Therapeutic effect of transplanting β 2 m − /Thy1 + bone marrow‐derived hepatocyte stem cells transduced with lentiviral‐mediated HGF gene into CCl 4 ‐injured rats
Author(s) -
Hu JunJie,
Sun Chao,
Lan Ling,
Chen YuanWen,
Li DingGuo
Publication year - 2010
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1439
Subject(s) - hepatocyte growth factor , stem cell , bone marrow , transplantation , bone marrow stem cell , genetic enhancement , cancer research , biology , hepatocyte , fibrosis , immunology , microbiology and biotechnology , pathology , in vitro , medicine , gene , biochemistry , receptor
Background β 2 m − /Thy1 + bone marrow‐derived hepatocyte stem cells (BDHSCs) isolated from the bone marrow of cholestatic rats by magnetic bead cell sorting consistently express characteristics of both stem and liver cells. These stem cells may be good vehicles for gene transfer. Administration of exogenous hepatocyte growth factor (HGF) may be potentially useful for the treatment of liver fibrosis. Because lentiviral vectors integrate stably into the host‐cell genome of nondividing and dividing cells, it may efficiently transfect β 2 m − /Thy1 + BDHSCs in vitro and secrete high‐level HGF consistently. Transplantation of β 2 m − /Thy1 + BDHSCs transduced with lentiviral vectors containing the HGF gene may reduce liver fibrosis in rats. Methods Lentiviral vectors expressing HGF were constructed and used to transduce β 2 m − /Thy1 + BDHSCs sorted from cholestatic rats in vitro . Transduction efficiency was evaluated and then these cells were transplanted into rats through the portal vein. Liver function as well as histological and immunohistochemical examinations were carried out to assess the therapeutic efficacy on liver fibrosis. Results We demonstrated that high‐level exogenous HGF was detected in supernatants after β 2 m − /Thy1 + BDHSCs were transfected with lentiviral vectors expressing HGF. Transplantation of transduced β 2 m − /Thy1 + BDHSCs significantly enhanced liver function and attenuated liver fibrosis in vivo . Conclusions The present study indicates that transplantation of β 2 m − /Thy1 + BDHSCs overexpressing the HGF gene may offer a novel approach for promoting liver function and reverse liver fibrosis. Copyright © 2010 John Wiley & Sons, Ltd.