Internal bioartificial liver with xenogeneic hepatocytes prevents death from acute liver failure: an experimental study.
OBJECTIVE
To demonstrate that a bioartificial liver, using allogeneic or xenogeneic hepatocytes protected from rejection by a semipermeable membrane, could prevent death from acute liver failure.


BACKGROUND
An implantable bioartificial liver using isolated hepatocytes could be an alternative to orthotopic liver transplantation to treat patients with acute liver failure. It could serve either as a bridge until liver transplantation or as the main treatment until recovery of the native liver. However, allogeneic or xenogeneic hepatocytes that could be used in clinical applications are spontaneously rejected.


METHODS
Acute liver failure was induced in rats by 95% liver resection. Twenty-five million hepatocytes harvested in rats (allogeneic) or guinea pigs (xenogeneic) were encapsulated in a semipermeable membrane to protect them from rejection. The hollow fibers containing hepatocytes were transplanted into the peritoneum of recipient rats. Survival rates were compared between rats transplanted or not with hepatocytes.


RESULTS
In groups not transplanted with viable hepatocytes, 73% to 93% of rats died after 95% liver resection. The mortality rate was reduced to 39% in rats transplanted with allogeneic hepatocytes and 36% in rats transplanted with xenogeneic hepatocytes. The bioartificial liver could be removed 1 month after transplantation, when regeneration of the native liver was complete. Allogeneic and xenogeneic hepatocytes remained viable.


CONCLUSIONS
The implantable bioartificial liver was able to prevent death in this model of acute liver failure. This could be an important step toward clinical application of the method.
Research Unit 402 of INSERM, the Department of Surgery, Hospital Saint-Antoine, Paris, France.
V
V
Roger
P
P
Balladur
J
J
Honiger
M
M
Baudrimont
R
R
Delelo
A
A
Robert
Y
Y
Calmus
J
J
Capeau
B
B
Nordlinger
D000818:Animals; D017690:Cell Transplantation; D004195:Disease Models, Animal; D006168:Guinea Pigs; D020007:Implants, Experimental; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology*; D017114:Liver Failure, Acute / Q000628:therapy*; D019164:Liver, Artificial; D008297:Male; D008567:Membranes, Artificial; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
D008567:Membranes, Artificial