Document Detail


No functional benefit for hDAF-transgenic rat livers despite protection from tissue damage following perfusion with human serum.
MedLine Citation:
PMID:  12478405     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Hein Stockmann; Caroline Verbakel; Petra Okkema; Fred Bonthuis; Severin Menoret; Ignacio Anegon; Richard Marquet; Jan IJzermans
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Publication Detail:
Type:  Journal Article     Date:  2002-10-19
Journal Detail:
Title:  Transplant international : official journal of the European Society for Organ Transplantation     Volume:  15     ISSN:  0934-0874     ISO Abbreviation:  Transpl. Int.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-12-12     Completed Date:  2003-09-02     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8908516     Medline TA:  Transpl Int     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  595-601     Citation Subset:  IM    
Affiliation:
Department of General Surgery, University Hospital Dijkzigt, 3000 CA Rotterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified
Antigens, CD / genetics
Antigens, CD55 / genetics*
Blood Physiological Phenomena
Blood Transfusion
Humans
Liver / pathology,  physiology*
Male
Perfusion / adverse effects
Rats
Rats, Sprague-Dawley
Rats, Wistar
Transplantation, Heterologous
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD55

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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