title: Growth ability and repopulation efficiency of transplanted hepatic stem cells, progenitor cells, and mature hepatocytes in retrorsine-treated rat livers.
abstract: Cell-based therapies as an alternative to liver transplantation have been anticipated for the treatment of potentially fatal liver diseases. Not only mature hepatocytes (MHs) but also hepatic stem/progenitor cells are considered as candidate cell sources. However, whether the stem/progenitor  cells have an advantage to engraft and repopulate the recipient liver compared with MHs has not been comprehensively assessed. Therefore, we used Thy1(+) (oval) and CD44(+) (small hepatocytes) cells isolated from GalN-treated rat livers as hepatic stem and progenitor cells,  respectively. Cells from dipeptidylpeptidase IV (DPPIV)(+) rat livers were transplanted into DPPIV(-) livers treated with retrorsine following partial hepatectomy. Both stem and progenitor cells could differentiate into hepatocytes in host livers. In addition, the growth  of the progenitor cells was faster than that of MHs until days 14. However, their repopulation efficiency in the long term was very low, since the survival period of the progenitor cells was much shorter than that of MHs. Most foci derived from Thy1(+) cells disappeared within 2 months.  Many cells expressed senescence-associated β-galactosidase in 33% of CD44-derived foci at day 60, whereas the expression was observed in 13% of MH-derived ones. The short life of the cells may be due to their cellular senescence. On the other hand, the incorporation of sinusoidal endothelial  cells into foci and sinusoid formation, which might be correlated to hepatic maturation, was completed faster in MH-derived foci than in CD44-derived ones. The survival of donor cells may have a close relation to not only early integration into hepatic plates but also the differentiated state  of the cells at the time of transplantation.
authors.affiliation: Department of Tissue Development and Regeneration, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Ichinohe
authors.forename: Junko
authors.initials: J
authors.lastname: Kon
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sasaki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ooe
authors.forename: Naoki
authors.initials: N
authors.lastname: Tanimizu
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Mitaka
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D016922:Cellular Senescence; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000601:surgery*; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006498:Hepatectomy; D022781:Hepatocytes / Q000637:transplantation*; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000601:surgery*; D008297:Male; D011763:Pyrrolizidine Alkaloids; D051381:Rats; D011916:Rats, Inbred F344; D033581:Stem Cell Transplantation; D013234:Stem Cells; D018800:Thy-1 Antigens / Q000096:biosynthesis; D001616:beta-Galactosidase / Q000096:biosynthesis
chemical_list: D018960:Hyaluronan Receptors; D011763:Pyrrolizidine Alkaloids; D018800:Thy-1 Antigens; D001616:beta-Galactosidase; D018819:Dipeptidyl Peptidase 4; C003300:retrorsine