Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 28, 2016; 8(33): 1442-1451
Published online Nov 28, 2016. doi: 10.4254/wjh.v8.i33.1442
Performance of cold-preserved rat liver Microorgans as the biological component of a simplified prototype model of bioartificial liver
María Dolores Pizarro, María Gabriela Mediavilla, Alejandra Beatriz Quintana, Ángel Luis Scandizzi, Joaquín Valentín Rodriguez, María Eugenia Mamprin
María Dolores Pizarro, Joaquín Valentín Rodríguez, Centro Binacional de Criobiología Clínica y Aplicada, Rosario 2000, Argentina
María Gabriela Mediavilla, Instituto de Biología Molecular y Celular de Rosario, Rosario 2000, Argentina
María Gabriela Mediavilla, Joaquín Valentín Rodriguez, María Eugenia Mamprin, Consejo Nacional de Investigaciones Científicas y Técnicas, Caba C1033AAJ, Argentina
Alejandra Beatriz Quintana, Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario 2000, Argentina
María Eugenia Mamprin, Ángel Luis Scandizzi, Área Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario S2002 LRK, Argentina
Author contributions: Pizarro MD performed the majority of experiments and analyzed the data; Mediavilla MG and Mamprin ME have designed research, performed research, contributed new reagents, analyzed data, wrote the manuscript; all the authors were involved in reviewing the literature for latest contributions in the field, writing, and edition of the manuscript; Mediavilla MG and Mamprin ME have equally contributed to this work.
Supported by Universidad Nacional de Rosario (UNR), No. 677/2013.
Institutional review board statement: The study was reviewed and approved by the National University of Rosario Institutional Review Board (Resol. C.S., No. 677/2013).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Faculty of Biochemical and Pharmaceutical Sciences-UNR (Resol. No. 139/2011).
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: María Eugenia Mamprin, PhD, Professor of Pharmacology, Área Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario S2002 LRK, Argentina. mmamprin@fbioyf.unr.edu.ar
Telephone: +54-341-4393400
Received: May 31, 2016
Peer-review started: June 1, 2016
First decision: July 20, 2016
Revised: July 28, 2016
Accepted: September 13, 2016
Article in press: September 18, 2016
Published online: November 28, 2016
Processing time: 177 Days and 10.6 Hours
Abstract
AIM

To develop a simplified bioartificial liver (BAL) device prototype, suitable to use freshly and preserved liver Microorgans (LMOs) as biological component.

METHODS

The system consists of 140 capillary fibers through which goat blood is pumped. The evolution of hematocrit, plasma and extra-fiber fluid osmolality was evaluated without any biological component, to characterize the prototype. LMOs were cut and cold stored 48 h in BG35 and ViaSpan® solutions. Fresh LMOs were used as controls. After preservation, LMOs were loaded into the BAL and an ammonia overload was added. To assess LMOs viability and functionality, samples were taken to determine lactate dehydrogenase (LDH) release and ammonia detoxification capacity.

RESULTS

The concentrations of ammonia and glucose, and the fluids osmolalities were matched after the first hour of perfusion, showing a proper exchange between blood and the biological compartment in the minibioreactor. After 120 min of perfusion, LMOs cold preserved in BG35 and ViaSpan® were able to detoxify 52.9% ± 6.5% and 53.6% ± 6.0%, respectively, of the initial ammonia overload. No significant differences were found with Controls (49.3% ± 8.8%, P < 0.05). LDH release was 6.0% ± 2.3% for control LMOs, and 6.2% ± 1.7% and 14.3% ± 1.1% for BG35 and ViaSpan® cold preserved LMOs, respectively (n = 6, P < 0.05).

CONCLUSION

This prototype relied on a simple design and excellent performance. It’s a practical tool to evaluate the detoxification ability of LMOs subjected to different preservation protocols.

Keywords: Rat liver Microorgans; Cold preservation; BG35 preservation solution; Bioartificial liver device; Acute liver failure

Core tip: This work describes the development of a simplified bioartiticial liver prototype (BAL, suitable to use rat liver Microorgans (LMOs) as biological component, and the evaluation of these tissue slices performance in this new model. We demonstrate that the minibioreactor constructed allows a good performance of fresh and cold preserved LMOs, showing the importance of architecture and model configuration on these devices design. Besides its application as BAL, this minibioreactor could serve as a suitable laboratory tool to evaluate the behavior and functionality of LMOs subjected to different preservation protocols due to its simple design and the utilization of standard materials.