Development of a new bioartificial liver using a porcine autologous biomatrix as hepatocyte support.
Long-term maintenance of hepatocyte viability and differentiated function expression is crucial for bioartificial liver support. The maintenance of hepatocyte function in a bioreactor is still a problem. A major advance was the recognition that hepatocytes in attachment cultures can maintain their differentiation longer. To restore hepatocyte polarity and prolong their function, we developed a new bioreactor with a cross-flow geometry configuration and an original hepatocyte extracellular autologous biomatrix (Porcine Bio-Matrix) support. To test this new bioreactor, we compared it with a standard bioartificial liver cartridge in a suitable surgical model of acute liver failure in pigs. In our model, we performed a total hepatectomy, followed by partial liver transplantation after an 18 hour anhepatic phase. The results showed that the bioreactor containing the biomatrix was able to bridge the animal to transplantation and to sustain the transplanted liver until all function recovered (80% of animals survived, p = 0.0027). No animal survived more than 24 hours after liver transplantation in the group treated with the traditional bioartificial liver, whereas hepatocyte viability on the Porcine Bio-Matrix was 65% after 12 hours of treatment. The results suggest that our biomatrix is a suitable cell support and guarantees long-term maintenance of metabolic activity of hepatocytes. Further studies are needed, but the results obtained with this new three-dimensional bioreactor are promising, and its potential is attractive.
Ambrosino
Giovanni
G
Department of Surgical and Gastroenterological Sciences, University of Padova, Italy.
Varotto
Sergio
S
Stefano Basso
S M
SM
Basso
M M Stefano
MM
Galavotri
Daniele
D
Cecchetto
Attilio
A
Carraro
Paolo
P
Naso
Agostino
A
De Silvestro
Giustina
G
Plebani
Mario
M
Giron
Gianpiero
G
Abatangelo
Giovanni
G
Donato
Daniele
D
Cestrone
Adriano
A
Marrelli
Luigi
L
Trombetta
Marcella
M
Lorenzelli
Vincenzo
V
Picardi
Antonio
A
Colantoni
Alessandra
A
Van Thiel
David
D
Ricordi
Camillo
C
D'Amico
Francesco Davide
FD
D000818:Animals; D019149:Bioreactors; D002470:Cell Survival; D005260:Female; D022781:Hepatocytes / Q000166:cytology*; D007668:Kidney / Q000502:physiology; D017114:Liver Failure, Acute / Q000401:mortality / Q000628:therapy*; D019164:Liver, Artificial; D013552:Swine