title: Development of a new bioartificial liver using a porcine autologous biomatrix as hepatocyte support.
abstract: 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.
authors.affiliation: Department of Surgical and Gastroenterological Sciences, University of Padova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ambrosino
authors.forename: Sergio
authors.initials: S
authors.lastname: Varotto
authors.forename: S M
authors.initials: SM
authors.lastname: Stefano Basso
authors.forename: M M Stefano
authors.initials: MM
authors.lastname: Basso
authors.forename: Daniele
authors.initials: D
authors.lastname: Galavotri
authors.forename: Attilio
authors.initials: A
authors.lastname: Cecchetto
authors.forename: Paolo
authors.initials: P
authors.lastname: Carraro
authors.forename: Agostino
authors.initials: A
authors.lastname: Naso
authors.forename: Giustina
authors.initials: G
authors.lastname: De Silvestro
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Giron
authors.forename: Giovanni
authors.initials: G
authors.lastname: Abatangelo
authors.forename: Daniele
authors.initials: D
authors.lastname: Donato
authors.forename: Adriano
authors.initials: A
authors.lastname: Cestrone
authors.forename: Luigi
authors.initials: L
authors.lastname: Marrelli
authors.forename: Marcella
authors.initials: M
authors.lastname: Trombetta
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lorenzelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Picardi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Colantoni
authors.forename: David
authors.initials: D
authors.lastname: Van Thiel
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
authors.forename: Francesco Davide
authors.initials: FD
authors.lastname: D'Amico
mesh_terms: 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