title: Hepatocyte transplantation and the differentiation fate of host oval cells in acute severe hepatic injury.
abstract: Oval cells and hepatocytes rarely proliferate simultaneously. This study aimed to determine the impacts of hepatocyte transplantation on the response and fate of oval cells that are activated to proliferate in acute severe hepatic injury. Retrorsine + D-galactosamine (R+D-gal) treatment was used to induce acute hepatic injury and to elicit extensive activation of oval cells in male dipeptidyl peptidase IV-deficient F344 rats. These rats were then randomized to receive wild-type hepatocyte transplantation or vehicle intraportally. The kinetics of oval cell response and their differentiation fate were analyzed. Results showed that oval cells were activated early and differentiated into hepatocytes in R+D-gal-treated rats without hepatocyte transplantation. With hepatocyte transplantation, the oval cells were recruited later and continued to proliferate in parallel with the massive proliferation of transplanted hepatocytes. They formed ductules and differentiated into biliary cells. When hepatocytes were transplanted at the day when oval cells were at their peak response, the numerous activated oval cells ceased to differentiate into hepatocytes and remained in ductular form. The ductular oval cells were capable of differentiating into hepatocytes again when the donor hepatocytes were inhibited to proliferate. We conclude that hepatocyte transplantation changes the mechanism of liver reconstitution and affects the differentiation fate of host oval cells in acute severe hepatic injury.
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chun-Hsien
authors.initials: CH
authors.lastname: Yu
authors.forename: Mei-Hwei
authors.initials: MH
authors.lastname: Chang
authors.forename: Chin-Sung
authors.initials: CS
authors.lastname: Chien
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Chen
authors.forename: Ming-Fu
authors.initials: MF
authors.lastname: Chang
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D002454:Cell Differentiation; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000601:surgery; D018819:Dipeptidyl Peptidase 4 / Q000172:deficiency; D005688:Galactosamine / Q000633:toxicity; D022781:Hepatocytes / Q000166:cytology / Q000637:transplantation*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000293:injuries*; D008297:Male; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011763:Pyrrolizidine Alkaloids; D005688:Galactosamine; D018819:Dipeptidyl Peptidase 4; C003300:retrorsine