title: Regeneration and Cell Recruitment in an Improved Heterotopic Auxiliary Partial Liver Transplantation Model in the Rat.
abstract: BACKGROUND
  Auxiliary partial liver transplantation (APLT) in humans is a therapeutic modality used especially to treat liver failure in children or congenital metabolic disease. Animal models of APLT have helped to explore therapeutic options. Though many groups have suggested improvements, standardizing the surgical procedure has been challenging. Additionally, the question of whether graft livers are reconstituted by recipient-derived cells after transplantation has been controversial. The aim of this study was to improve experimental APLT in rats and to assess cell recruitment in the liver grafts.
  
  
  METHODS
  To inhibit recipient liver regeneration and to promote graft regeneration, we treated recipients with retrorsine and added arterial anastomosis. Using green fluorescence protein transgenic rats as recipients, we examined liver resident cell recruitment within graft livers by immunofluorescence costaining.
  
  
  RESULTS
  In the improved APLT model, we achieved well-regenerated grafts that could maintain regeneration for at least 4 weeks. Regarding the cell recruitment, there was no evidence of recipient-derived hepatocyte, cholangiocyte, or hepatic stellate cell recruitment into the graft. Macrophages/monocytes, however, were consistently recruited into the graft and increased over time, which might be related to inflammatory responses. Very few endothelial cells showed colocalization of markers.
  
  
  CONCLUSIONS
  We have successfully established an improved rat APLT model with arterial anastomosis as a standard technique. Using this model, we have characterized cell recruitment into the regenerating grafts.
authors.affiliation: 1 Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.2 Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan.3 Thomas E Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA.4 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ono
authors.forename: Angelica
authors.initials: A
authors.lastname: Pérez-Gutiérrez
authors.forename: Mladen I
authors.initials: MI
authors.lastname: Yovchev
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsubara
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yokota
authors.forename: Jorge
authors.initials: J
authors.lastname: Guzman-Lepe
authors.forename: Kan
authors.initials: K
authors.lastname: Handa
authors.forename: Alexandra
authors.initials: A
authors.lastname: Collin de l'Hortet
authors.forename: Angus W
authors.initials: AW
authors.lastname: Thomson
authors.forename: David A
authors.initials: DA
authors.lastname: Geller
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagi
authors.forename: Michael
authors.initials: M
authors.lastname: Oertel
authors.forename: Alejandro
authors.initials: A
authors.lastname: Soto-Gutierrez
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008115:Liver Regeneration / Q000187:drug effects; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D023421:Models, Animal; D011763:Pyrrolizidine Alkaloids / Q000494:pharmacology; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D013997:Time Factors
chemical_list: D011763:Pyrrolizidine Alkaloids; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C003300:retrorsine