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.
Hu
Jun-Jie
JJ
Department of Gastroenterology, Xinhua Hospital, College of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Sun
Chao
C
Lan
Ling
L
Chen
Yuan-Wen
YW
Li
Ding-Guo
DG
D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D002251:Carbon Tetrachloride / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D022781:Hepatocytes / Q000637:transplantation*; D016086:Lentivirus; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D018800:Thy-1 Antigens / Q000032:analysis; D014161:Transduction, Genetic; D001613:beta 2-Microglobulin / Q000032:analysis
D018800:Thy-1 Antigens; D001613:beta 2-Microglobulin; D017228:Hepatocyte Growth Factor; D002251:Carbon Tetrachloride