title: Replacement of liver parenchyma in analbuminemic rats with allogenic hepatocytes is facilitated by intrabone marrow-bone marrow transplantation.
abstract: Although hepatocyte transplantation (HCTx) is expected to become a useful therapy for human liver diseases, allogenic hepatocytes still tend to be rejected within a short period due to host immunosurveillance. In the present study, we investigated the effect of prior bone marrow transplantation  (BMTx) for the engraftment of allogenic hepatocytes using the analbuminemic rat transplantation model. The hepatocytes of Lewis (LEW) rats were not accepted in the liver of retrorsine (RS)/partial hepatectomy (PH)-treated analbuminemic F344 (F344-alb) rats, which express the disparate major  histocompatibility complex (MHC) against that of LEW rats. Prior BMTx with the LEW bone marrow cells (BMCs) after sublethal irradiation achieved acceptance and repopulation of LEW hepatocytes in the liver of the RS/PH-treated F344-alb rats, associated with elevation of serum albumin. The replacement  of hepatic parenchyma with albumin positive (Alb(+)) donor hepatocytes and elevation of serum albumin levels were dependent on the bone marrow reconstitution by donor BMCs, which was more efficiently achieved by intrabone marrow (IBM)-BMTx than by intravenous (IV)-BMTx. Our results  demonstrate that efficient bone marrow reconstitution by IBM-BMTx enables the replacement of the hepatic parenchyma with allogenic hepatocytes in RS/PH-treated analbuminemic rats without immunosuppressants.
authors.affiliation: Department of Surgery, Asahikawa Medical University, Asahikawa, Japan. inagaki@asahikawa-med.ac.jp
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Inagaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Furukawa
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Satake
authors.forename: Yoko
authors.initials: Y
authors.lastname: Okada
authors.forename: Shinichi
authors.initials: S
authors.lastname: Chiba
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishikawa
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D022781:Hepatocytes / Q000378:metabolism / Q000637:transplantation*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012709:Serum Albumin / Q000378:metabolism*; D016019:Survival Analysis; D014184:Transplantation, Homologous
chemical_list: D012709:Serum Albumin