title: No functional benefit for hDAF-transgenic rat livers despite protection from tissue damage following perfusion with human serum.
abstract: Currently, xenogeneic extracorporeal liver perfusion is used in the treatment of acute liver failure. In order to determine whether transgeneity for human regulatory proteins could improve the functional outcome of the ex-vivo liver in relation to the histopathological changes, we studied the effect of the humoral mechanism in xenogeneic isolated rat liver perfusion in normal and transgenic rat livers. Isolated rat liver perfusion was performed for 2 h in normal rat livers with Krebs Henseleit (KH) and human serum (HS), and in livers transgenic for human decay accelerating factor (hDAF; Tg HS). Function of the liver was established by measurement of liver enzymes and bile production, and clearance of bromosulphophthalein (BSP). Tissue specimens taken after perfusion were analysed by routine histology and immunofluorescence staining for C3c deposition. No change in release of liver enzymes could be established throughout the perfusion period. In the 2nd hour, a higher level of bile production was seen for the transgenic group than for the HS group. The transgenic rat livers outperformed the normal livers perfused with HS, when BSP concentration in the bile was measured; however, clearance of BSP from the perfusate was not significantly different. Haematoxylin-eosin (HE) staining of the liver tissue showed evidence of hyperacute rejection in the HS group. There was only mild tissue injury in the transgenic liver. High-intensity fluorescent staining for C3c deposition was seen in the normal livers perfused with HS, and significantly less in the transgenic livers. Although histologically less tissue damage and less C3c deposition was shown, no significantly improved function of the livers transgenic for hDAF was established. These results suggest that for short-term extracorporeal liver perfusion transgenesis offers no functional benefit.
authors.affiliation: Department of General Surgery, University Hospital Dijkzigt, 3000 CA Rotterdam, The Netherlands.
authors.forename: Hein
authors.initials: H
authors.lastname: Stockmann
authors.forename: Caroline
authors.initials: C
authors.lastname: Verbakel
authors.forename: Petra
authors.initials: P
authors.lastname: Okkema
authors.forename: Fred
authors.initials: F
authors.lastname: Bonthuis
authors.forename: Severin
authors.initials: S
authors.lastname: Menoret
authors.forename: Ignacio
authors.initials: I
authors.lastname: Anegon
authors.forename: Richard
authors.initials: R
authors.lastname: Marquet
authors.forename: Jan
authors.initials: J
authors.lastname: IJzermans
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000235:genetics; D001790:Blood Physiological Phenomena; D001803:Blood Transfusion; D018958:CD55 Antigens / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000473:pathology / Q000502:physiology*; D008297:Male; D010477:Perfusion / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014183:Transplantation, Heterologous
chemical_list: D015703:Antigens, CD; D018958:CD55 Antigens