Therapeutic effect of transplanting beta(2)m(-)/Thy1(+) bone marrow-derived hepatocyte stem cells transduced with lentiviral-mediated HGF gene into CCl(4)-injured rats.

Background: beta(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 beta(2)m(-)/Thy1(+) BDHSCs in vitro and secrete high-level HGF consistently. Transplantation of beta(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 beta(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 beta(2)m(-)/Thy1(+) BDHSCs were transfected with lentiviral vectors expressing HGF. Transplantation of transduced beta(2)m(-)/Thy1(+) BDHSCs significantly enhanced liver function and attenuated liver fibrosis in vivo.

Conclusions: The present study indicates that transplantation of beta(2)m(-)/Thy1(+) BDHSCs overexpressing the HGF gene may offer a novel approach for promoting liver function and reverse liver fibrosis.