A bioartificial liver support system using primary hepatocytes: a preclinical study in a new porcine hepatectomy model.
BACKGROUND
Bioartificial liver support systems providing a bridge to transplantation or even a definitive treatment of acute hepatic failure are a current focus of research. Different devices are used, although an impact on patient survival is doubtful for the time being. After developing a new flat membrane bioreactor, further preclinical studies have become necessary. Existing animal models of fulminant hepatic failure show common difficulties in defining a reproducible loss of functional liver tissue while considering systemic side effects. We now present a reproducible model with total hepatectomy in pigs, suitable to test the safety and efficacy of liver support systems.


METHODS
Twelve pigs underwent total hepatectomy by using silicone tubes and a Y-adapter as vascular prosthesis; intracranial pressure was measured via a subdural probe. Anhepatic pigs were monitored under general anesthesia until death occurred. All were treated with a new flat membrane bioreactor (FMB) that contained porcine hepatocytes in 6 of the 12 cases.


RESULTS
Our hepatectomy technique proved to be successful without requiring venovenous bypass circulation. Mean vascular clamping time was 9 minutes. The mean survival time was longer in animals treated with hepatocyte-equipped bioreactors than in untreated animals (24.8 +/- 4.3 vs 16.4 +/- 4.7 hours), which already showed increased intracranial pressure after 10 to 12 hours. Serum albumin levels indicated stable cell-specific functions of the FMB.


CONCLUSIONS
The described technique of total hepatectomy is a well-reproducible animal model. The presented FMB maintained stable cell-specific functions and is a safe and efficient device.
Frühauf
Nils R
NR
Department of General Surgery and Transplantation, University of Essen, Germany.
Oldhafer
Karl J
KJ
Höltje
Maike
M
Kaiser
Gernot M
GM
Frühauf
Jan-Henning
JH
Stavrou
Gregor A
GA
Bader
Augustinus
A
Broelsch
Christoph E
CE
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects*; D022781:Hepatocytes / Q000502:physiology*; D017114:Liver Failure, Acute / Q000209:etiology / Q000628:therapy*; D019164:Liver, Artificial; D008567:Membranes, Artificial; D023421:Models, Animal; D015203:Reproducibility of Results; D013552:Swine; D016896:Treatment Outcome
D008567:Membranes, Artificial