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A clinical-scale BioArtificial Liver, developed for GMP, improved clinical parameters of liver function in porcine liver failure

Selden, C; Bundy, J; Erro, E; Puschmann, E; Miller, M; Kahn, D; Hodgson, H; ... Spearman, CW; + view all (2017) A clinical-scale BioArtificial Liver, developed for GMP, improved clinical parameters of liver function in porcine liver failure. Scientific Reports , 7 , Article 14518. 10.1038/s41598-017-15021-4. Green open access

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Abstract

Liver failure, whether arising directly from acute liver failure or from decompensated chronic liver disease is an increasing problem worldwide and results in many deaths. In the UK only 10% of individuals requiring a liver transplant receive one. Thus the need for alternative treatments is paramount. A BioArtificial Liver machine could temporarily replace the functions of the liver, buying time for the patient’s liver to repair and regenerate. We have designed, implemented and tested a clinical-scale BioArtificial Liver machine containing a biomass derived from a hepatoblastoma cell-line cultured as three dimensional organoids, using a fluidised bed bioreactor, together with single-use bioprocessing equipment, with complete control of nutrient provision with feedback BioXpert recipe processes, and yielding good phenotypic liver functions. The methodology has been designed to meet specifications for GMP production, required for manufacture of advanced therapy medicinal products (ATMPs). In a porcine model of severe liver failure, damage was assured in all animals by surgical ischaemia in pigs with human sized livers (1.2–1.6 kg liver weights). The BioArtificial liver (UCLBAL) improved important prognostic clinical liver-related parameters, eg, a significant improvement in coagulation, reduction in vasopressor requirements, improvement in blood pH and in parameters of intracranial pressure (ICP) and oxygenation.

Type: Article
Title: A clinical-scale BioArtificial Liver, developed for GMP, improved clinical parameters of liver function in porcine liver failure
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-017-15021-4
Publisher version: http://doi.org/10.1038/s41598-017-15021-4
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, FLUIDIZED-BED BIOREACTOR, HEPATOCYTE CELL-LINES, ACUTE HEPATIC-FAILURE, CONTROLLED-TRIAL, PLASMA-EXCHANGE, MASS TRANSFERS, CHAIN DELIVERY, ALGINATE BEADS, SUPPORT-SYSTEM, ANIMAL-MODELS
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/10039552
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