Cold Storage of Liver Microorgans (LMOs) in ViaSpan® and BG35 Solutions. Analysis of Urea Cycle Enzymes and Amonnia Detoxification for use as Biological Component of a BAL System.

PIZARRO D.; MEDIAVILLA M.G.; BERARDI F.; TIRIBELI C.; RODRÍGUEZ J.V.; MAMPRIN M.E.

ANNALS OF HEPATOLOGY

MEXICAN ASSOC HEPATOLOGY

Lugar: Mexico, DF.; Año: 2013

1665-2681

Bioartificial Livers (BAL) were designed as a bridge to maintain patients with liver failure. In these devices, the patient´s blood is circulated extra-corporeally through a bioreactor that houses a metabolically active component, as isolated hepatic cells or cultured cells. We have recently become interested in evaluating the performance of rat Liver Microorgans. We have developed a novel preservation solution, BG35, to protect LMOs against cold injury. This would allow having the biological component viable to be used when is needed for our BAL. The Urea Cycle is the major pathway of ammonia removal, the objective of this work was to study gene expression and activity of CPSI and OTC, two key enzymes, after LMOs preservation in BG35 and ViaSpan®. We have assayed in vitro the LMOs ability to detoxify an overload of ammonia in order to evaluate them for their successive application into a BAL. LMOs were stored at 0°C in BG35 or ViaSpan®. The preservation conditions did not affect ammonia metabolism: LMOs cold preserved in BG35 and ViaSpan® could detoxify 29.3±7.9 % and 25.7±4.9 % of the initial overload, similarly than Controls (29.7±10.7 %). Though there were differences in relative mRNA levels between Controls and the two preserved groups, the values of CPSI and OTC enzymatic activity were comparable in all studied groups. In conclusion, we demonstrate that our preservation conditions did not affect ammonia metabolism and cold preserved LMOs maintain the physiological and biochemical liver functions tested, which allows their use as biological component of a BAL system.