title: Construction of liver tissue in vivo with preparative partial hepatic irradiation and growth stimulus: investigations of less invasive techniques and progenitor cells.
abstract: BACKGROUND
  The selective proliferation of transplanted hepatocytes with a growth stimulus, such as partial hepatectomy or hepatocyte growth factor, concomitant with hepatic irradiation (HIR), which can suppress proliferation of host hepatocytes, has been reported. We have conducted experiments that focused on less invasive and clinically applicable techniques and progenitor cells.
  
  
  METHODS
  First, dipeptidyl-peptidase IV-F344 or jaundiced Gunn rats underwent partial HIR (only 30% of whole liver) and portal vein branch ligation (PVBL) of one lobe, followed by intrasplenic hepatocyte transplantation at 1 × 10(7). Second, after partial HIR and PVBL, two types of progenitor cells were transplanted (i.e., small hepatocytes (SHs) or adipose-derived mesenchymal stem cells.
  
  
  RESULTS
  Sixteen weeks after transplantation, the donor cells constituted > 70% of the hepatocytes of the irradiated lobe, showing connexin 32, phosphoenolpyruvate carboxykinase-1, and glycogen storage. Moreover, the serum bilirubin level had decreased significantly in the jaundiced Gunn rats and remained at this level throughout the 24 wk experimental period. The SHs grew more quickly than the hepatocytes. After 8 wk, around 40% of the host hepatocytes had been replaced by transplanted SHs. Although the donor adipose-derived mesenchymal cells were engrafted after 8 wk, their proliferation was not observed.
  
  
  CONCLUSIONS
  HIR, combined with PVBL, can be given to a selective liver lobe and is a less-invasive but effective method for proliferation of transplanted hepatocytes. Even a smaller number of SHs can construct liver tissue with their prevailing proliferative ability.
authors.affiliation: Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Kosho
authors.initials: K
authors.lastname: Yamanouchi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sakai
authors.forename: Izumi
authors.initials: I
authors.lastname: Yamaguchi
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Takatsuki
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kuroki
authors.forename: Chandan
authors.initials: C
authors.lastname: Guha
authors.forename: Susumu
authors.initials: S
authors.lastname: Eguchi
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D049109:Cell Proliferation; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics; D006085:Graft Survival / Q000502:physiology; D022781:Hepatocytes / Q000528:radiation effects / Q000637:transplantation*; D008026:Ligation; D008099:Liver / Q000166:cytology* / Q000254:growth & development / Q000528:radiation effects; D008107:Liver Diseases / Q000503:physiopathology / Q000628:therapy*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D011169:Portal Vein; D051381:Rats; D011911:Rats, Gunn; D011916:Rats, Inbred F344; D011922:Rats, Mutant Strains
chemical_list: D018819:Dipeptidyl Peptidase 4
keywords: Adipose-derived mesenchymal stem cell; Hepatic irradiation; Hepatocyte transplantation; Portal vein branch ligation; Small hepatocyte