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

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 paramoun...

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Autores principales: Selden, Clare, Bundy, James, Erro, Eloy, Puschmann, Eva, Miller, Malcolm, Kahn, Delawir, Hodgson, Humphrey, Fuller, Barry, Gonzalez-Molina, Jordi, Le Lay, Aurelie, Gibbons, Stephanie, Chalmers, Sherri, Modi, Sunil, Thomas, Amy, Kilbride, Peter, Isaacs, Agnes, Ginsburg, Richard, Ilsley, Helen, Thomson, David, Chinnery, Galya, Mankahla, Ncedile, Loo, Lizel, Spearman, C. Wendy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674071/
https://www.ncbi.nlm.nih.gov/pubmed/29109530
http://dx.doi.org/10.1038/s41598-017-15021-4
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author Selden, Clare
Bundy, James
Erro, Eloy
Puschmann, Eva
Miller, Malcolm
Kahn, Delawir
Hodgson, Humphrey
Fuller, Barry
Gonzalez-Molina, Jordi
Le Lay, Aurelie
Gibbons, Stephanie
Chalmers, Sherri
Modi, Sunil
Thomas, Amy
Kilbride, Peter
Isaacs, Agnes
Ginsburg, Richard
Ilsley, Helen
Thomson, David
Chinnery, Galya
Mankahla, Ncedile
Loo, Lizel
Spearman, C. Wendy
author_facet Selden, Clare
Bundy, James
Erro, Eloy
Puschmann, Eva
Miller, Malcolm
Kahn, Delawir
Hodgson, Humphrey
Fuller, Barry
Gonzalez-Molina, Jordi
Le Lay, Aurelie
Gibbons, Stephanie
Chalmers, Sherri
Modi, Sunil
Thomas, Amy
Kilbride, Peter
Isaacs, Agnes
Ginsburg, Richard
Ilsley, Helen
Thomson, David
Chinnery, Galya
Mankahla, Ncedile
Loo, Lizel
Spearman, C. Wendy
author_sort Selden, Clare
collection PubMed
description 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.
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spelling pubmed-56740712017-11-15 A clinical-scale BioArtificial Liver, developed for GMP, improved clinical parameters of liver function in porcine liver failure Selden, Clare Bundy, James Erro, Eloy Puschmann, Eva Miller, Malcolm Kahn, Delawir Hodgson, Humphrey Fuller, Barry Gonzalez-Molina, Jordi Le Lay, Aurelie Gibbons, Stephanie Chalmers, Sherri Modi, Sunil Thomas, Amy Kilbride, Peter Isaacs, Agnes Ginsburg, Richard Ilsley, Helen Thomson, David Chinnery, Galya Mankahla, Ncedile Loo, Lizel Spearman, C. Wendy Sci Rep Article 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. Nature Publishing Group UK 2017-11-06 /pmc/articles/PMC5674071/ /pubmed/29109530 http://dx.doi.org/10.1038/s41598-017-15021-4 Text en © The Author(s) 2017 Open Access 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/.
spellingShingle Article
Selden, Clare
Bundy, James
Erro, Eloy
Puschmann, Eva
Miller, Malcolm
Kahn, Delawir
Hodgson, Humphrey
Fuller, Barry
Gonzalez-Molina, Jordi
Le Lay, Aurelie
Gibbons, Stephanie
Chalmers, Sherri
Modi, Sunil
Thomas, Amy
Kilbride, Peter
Isaacs, Agnes
Ginsburg, Richard
Ilsley, Helen
Thomson, David
Chinnery, Galya
Mankahla, Ncedile
Loo, Lizel
Spearman, C. Wendy
A clinical-scale BioArtificial Liver, developed for GMP, improved clinical parameters of liver function in porcine liver failure
title A clinical-scale BioArtificial Liver, developed for GMP, improved clinical parameters of liver function in porcine liver failure
title_full A clinical-scale BioArtificial Liver, developed for GMP, improved clinical parameters of liver function in porcine liver failure
title_fullStr A clinical-scale BioArtificial Liver, developed for GMP, improved clinical parameters of liver function in porcine liver failure
title_full_unstemmed A clinical-scale BioArtificial Liver, developed for GMP, improved clinical parameters of liver function in porcine liver failure
title_short A clinical-scale BioArtificial Liver, developed for GMP, improved clinical parameters of liver function in porcine liver failure
title_sort clinical-scale bioartificial liver, developed for gmp, improved clinical parameters of liver function in porcine liver failure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674071/
https://www.ncbi.nlm.nih.gov/pubmed/29109530
http://dx.doi.org/10.1038/s41598-017-15021-4
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