Experimental bio-artificial liver:Importance of the architectural design on ammonia detoxification performance  

作　　者：María Dolores Pizarro María Eugenia Mamprin Lucas Damián Daurelio Joaquín Valentín Rodriguez María Gabriela Mediavilla 

机构地区：[1]Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET),Rosario S2002 LRK,Argentina [2]Laboratorio de Investigaciones en Fisiología y Biología Molecular Vegetal(LIFiBVe),Facultad de Ciencias Agrarias,Universidad Nacional del Litoral,Esperanza 3080,Argentina [3]Facultad de Ciencias Bioquímicas y Farmacéuticas,Universidad Nacional de Rosario,Rosario S2002 LRK,Argentina [4]Centro Binacional de Criobiología Clínica y Aplicada(CAIC),Universidad Nacional de Rosario,Rosario S2011 BXN,Argentina [5]Instituto de Biología Molecular y Celular de Rosario(IBR,CONICET-UNR),Consejo Nacional de Investigaciones Científicas y Tecnológicas,y Universidad Nacional de Rosario,Rosario S2002 LRK,Argentina

出　　处：《World Journal of Hepatology》2018年第10期719-730,共12页世界肝病学杂志（英文版）（电子版）

基　　金：Supported by Universidad Nacional de Rosario(UNR),BIO 272,Resol.C.S.,No.677/2013;Agencia Nacional de Promoción Científica y Tecnológica(ANPCyT),PICT-03-14492,BID 1728 OC/AR(Argentina);a grant from Regione Autonoma FriuliVenezia Giulia,Italy

摘　　要：AIM To determine the influence of the construction design over the biological component's performance in an experimental bio-artificial liver(BAL) device.METHODS Two BAL models for liver microorgans(LMOs) were constructed. First, we constructed a cylindrical BAL and tested it without the biological component to establish its correct functioning. Samples of blood and biological compartment(BC) fluid were taken after 0, 60, and 120 min of perfusion. Osmolality, hematocrit, ammonia and glucose concentrations, lactate dehydrogenase(LDH) release(as a LMO viability parameter), and oxygen consumption and ammonia metabolizing capacity(as LMO functionality parameters) were determined. CPSI and OTC gene expression and function were measured. The second BAL, a "flat bottom" model, was constructed using a 25 cm2 culture flask while maintaining all other components between the models. The BC of both BALs had the same capacity(approximately 50 cm3) and both were manipulated with the same perfusion system. The performances of the two BALs were compared to show the influence of architecture.RESULTS The cylindrical BAL showed a good exchange of fluids and metabolites between blood and the BC, reflected by the matching of osmolalities, and glucose and ammonia concentration ratios after 120 min of perfusion. No hemoconcentration was detected, the hematocrit levels remained stable during the whole study, and the minimal percentage of hemolysis(0.65% ± 0.10%) observed was due to the action of the peristaltic pump. When LMOs were used as biological component of this BAL they showed similar values to the ones obtained in a Normothermic Reoxygenation System(NRS) for almost all the parameters assayed. After 120 min, the results obtained were: LDH release(%): 14.7 ± 3.1 in the BAL and 15.5 ± 3.2 in the NRS(n = 6); oxygen consumption(μmol/min?g wet tissue): 1.16 ± 0.21 in the BAL and 0.84 ± 0.15 in the NRS(n = 6); relative expression of Cps1 and Otc: 0.63 ± 0.12 and 0.67 ± 0.20, respectively, in the BAL, and 0.86 ± 0.10 and 0.82 �AIM To determine the influence of the construction design over the biological component's performance in an experimental bio-artificial liver(BAL) device.METHODS Two BAL models for liver microorgans(LMOs) were constructed. First, we constructed a cylindrical BAL and tested it without the biological component to establish its correct functioning. Samples of blood and biological compartment(BC) fluid were taken after 0, 60, and 120 min of perfusion. Osmolality, hematocrit, ammonia and glucose concentrations, lactate dehydrogenase(LDH) release(as a LMO viability parameter), and oxygen consumption and ammonia metabolizing capacity(as LMO functionality parameters) were determined. CPSI and OTC gene expression and function were measured. The second BAL, a "flat bottom" model, was constructed using a 25 cm2 culture flask while maintaining all other components between the models. The BC of both BALs had the same capacity(approximately 50 cm3) and both were manipulated with the same perfusion system. The performances of the two BALs were compared to show the influence of architecture.RESULTS The cylindrical BAL showed a good exchange of fluids and metabolites between blood and the BC, reflected by the matching of osmolalities, and glucose and ammonia concentration ratios after 120 min of perfusion. No hemoconcentration was detected, the hematocrit levels remained stable during the whole study, and the minimal percentage of hemolysis(0.65% ± 0.10%) observed was due to the action of the peristaltic pump. When LMOs were used as biological component of this BAL they showed similar values to the ones obtained in a Normothermic Reoxygenation System(NRS) for almost all the parameters assayed. After 120 min, the results obtained were: LDH release(%): 14.7 ± 3.1 in the BAL and 15.5 ± 3.2 in the NRS(n = 6); oxygen consumption(μmol/min?g wet tissue): 1.16 ± 0.21 in the BAL and 0.84 ± 0.15 in the NRS(n = 6); relative expression of Cps1 and Otc: 0.63 ± 0.12 and 0.67 ± 0.20, respectively, in the BAL, and 0.86 ± 0.10 and 0.82 �

关 键 词：Bio-artificial LIVER AMMONIA DETOXIFICATION Device design ORNITHINE Transcarbamylase Rat LIVER microorgans Carbamyl Phosphate SynthetaseⅠ 

分 类 号：R[医药卫生]