Performance of cold-preserved rat liver Microorgans as the biological component of a simplified prototype model of bioartificial liver

Pizarro, María Dolores; Mediavilla, María Gabriela; Quintana, Alejandra; Scandizzi, Angel L.; Rodriguez, Joaquı́n V.; Mamprin, María Eugenia

doi:10.4254/wjh.v8.i33.1442

Cited by 1 publication

(7 citation statements)

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“…Testing with LMOs as a biological component to determine the influence of the BAL configuration and design over the LMO ammonia detoxification capacity. Other parameters remained similar to the values encountered for the cylindrical BAL and were already published[ 15 ].…”

Section: Methodssupporting

confidence: 71%

“…Ammonia detoxification was the key task that LMOs could not perform in the cylindrical shape BAL. When they were evaluated in the “flat bottom” BAL, fresh LMOs were able to metabolize 32.1% ± 2.2% and 49.3% ± 8.8% of the initial NH 4 + dose at 60 min and 120 min, respectively ( n = 6 different LMO preparations in independent runs)[ 15 ], results that support the importance of architecture.…”

Section: Resultsmentioning

confidence: 98%

“…All the other components and materials utilized were the same in both devices, including the perfusion system. This “flat bottom” BAL performed well in experiments without a biological component[ 15 ].…”

Section: Resultsmentioning

confidence: 99%

“…When we tested fresh LMO ammonia detoxification efficiency in this new “flat bottom” BAL, the results obtained supported our hypothesis. They were able to detoxify 49.3% ± 8.8% of the initial ammonia overload after 120 min of perfusion[ 15 ], contrary to the LMOs applied to the cylindrical BAL (Table 7 ). This observation demonstrates the importance of adjusting the architecture and design of the artificial compartment to a given biological component in order to obtain an optimal BAL performance.…”

Section: Discussionmentioning

confidence: 99%

“…We constructed a device with a flat base BC using a standard 25 cm 2 culture flask[ 15 ] as shown in Figure 2C . The culture flask was adapted introducing a Y-shape connector (Nalgene, # 6152–0375) onto its tap and a plain connector (S/P silicone tube, 6.4 mm i.d., 11.2 mm o.d., and 2.4 mm wall) on one side, to assemble the 140 hollow fibers (Polyamix TM , GAMBRO ® ).…”

Section: Methodsmentioning

confidence: 99%

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

Pizarro¹,

Mamprin²,

Daurelio³

et al. 2018

WJH

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AIMTo determine the influence of the construction design over the biological component’s performance in an experimental bio-artificial liver (BAL) device.METHODSTwo 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.RESULTSThe 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 ± 0.07, respectively, in the NRS (n = 3); enzymatic activity of CPSI and OTC (U/g wet tissue): 3.03 ± 0.86 and 222.0 ± 23.5, respectively, in the BAL, and 3.12 ± 0.73 and 228.8 ± 32.8, respectively, in the NRS (n = 3). In spite of these similarities, LMOs as a biological component of the cylindrical BAL were not able to detoxify ammonia at a significant level (not detected vs 35.1% ± 7.0% of the initial 1 mM NH4+ dose in NRS, n = 6). Therefore, we built a second BAL with an entirely different design that offers a flat base BC. When LMOs were placed in this “flat bottom” device they were able to detoxify 49.3% ± 8.8% of the initial ammonia overload after 120 min of perfusion (n = 6), with a detoxification capacity of 13.2 ± 2.2 μmol/g wet tissue.CONCLUSIONIn this work, we demonstrate the importance of adapting the BAL architecture to the biological component characteristics to obtain an adequate BAL performance.

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Section: Methodssupporting

confidence: 71%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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