Evaluation of encapsulated liver cell spheroids in a fluidised-bed bioartificial liver for treatment of ischaemic acute liver failure in pigs in a translational setting

 

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dc.contributor.author Selden, Clare en_ZA
dc.contributor.author Spearman, Catherine Wendy en_ZA
dc.contributor.author Kahn, Delawir en_ZA
dc.contributor.author Miller, Malcolm en_ZA
dc.contributor.author Figaji, Anthony en_ZA
dc.contributor.author Erro, Eloy en_ZA
dc.contributor.author Bundy, James en_ZA
dc.contributor.author Massie, Isobel en_ZA
dc.contributor.author Chalmers, Sherri-Ann en_ZA
dc.contributor.author Arendse, Hiram en_ZA
dc.date.accessioned 2015-11-23T12:29:40Z
dc.date.available 2015-11-23T12:29:40Z
dc.date.issued 2013 en_ZA
dc.identifier.citation Selden, C., Spearman, C. W., Kahn, D., Miller, M., Figaji, A., Erro, E., ... & Hodgson, H. (2012). Evaluation of encapsulated liver cell spheroids in a fluidised-bed bioartificial liver for treatment of ischaemic acute liver failure in pigs in a translational setting. PloS one, 8(12), e82312. doi:10.1371/journal.pone.0082312 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/15299
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0082312
dc.description.abstract Liver failure is an increasing problem. Donor-organ shortage results in patients dying before receiving a transplant. Since the liver can regenerate, alternative therapies providing temporary liver-support are sought. A bioartificial-liver would temporarily substitute function in liver failure buying time for liver regeneration/organ-procurement. Our aim: to develop a prototype bioartificial-liver-machine (BAL) comprising a human liver-derived cell-line, cultured to phenotypic competence and deliverable in a clinical setting to sites distant from its preparation. The objective of this study was to determine whether its use would improve functional parameters of liver failure in pigs with acute liver failure, to provide proof-of-principle. HepG2cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4-6×10 10 cells, were transported from preparation-laboratory to point-of-use operating theatre (6000miles) under perfluorodecalin at ambient temperature. Irreversible ischaemic liver failure was induced in anaesthetised pigs, after portal-systemic-shunt, by hepatic-artery-ligation. Biochemical parameters, intracranial pressure, and functional-clotting were measured in animals connected in an extracorporeal bioartificial-liver circuit. Efficacy was demonstrated comparing outcomes between animals connected to a circuit containing alginate-encapsulated cells (Cell-bead BAL), and those connected to circuit containing alginate capsules without cells (Empty-bead BAL). Cells of the biomass met regulatory standards for sterility and provenance. All animals developed progressive liver-failure after ischaemia induction. Efficacy of BAL was demonstrated since animals connected to a functional biomass (+ cells) had significantly smaller rises in intracranial pressure, lower ammonia levels, more bilirubin conjugation, improved acidosis and clotting restoration compared to animals connected to the circuit without cells. In the +cell group, human proteins accumulated in pigs' plasma. Delivery of biomass using a short-term cold-chain enabled transport and use without loss of function over 3days. Thus, a fluidised-bed bioreactor containing alginate-encapsulated HepG2cell-spheroids improved important parameters of acute liver failure in pigs. The system can readily be up-scaled and transported to point-of-use justifying development at clinical scale. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other Acute liver failure en_ZA
dc.subject.other Swine en_ZA
dc.subject.other Blood plasma en_ZA
dc.subject.other Liver transplantation en_ZA
dc.subject.other Albumins en_ZA
dc.subject.other Ammonia en_ZA
dc.subject.other Ischemia en_ZA
dc.subject.other Bilirubin en_ZA
dc.title Evaluation of encapsulated liver cell spheroids in a fluidised-bed bioartificial liver for treatment of ischaemic acute liver failure in pigs in a translational setting en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2013 Selden et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Hepatology en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Selden, C., Spearman, C. W., Kahn, D., Miller, M., Figaji, A., Erro, E., ... Arendse, H. (2013). Evaluation of encapsulated liver cell spheroids in a fluidised-bed bioartificial liver for treatment of ischaemic acute liver failure in pigs in a translational setting. <i>PLoS One</i>, http://hdl.handle.net/11427/15299 en_ZA
dc.identifier.chicagocitation Selden, Clare, Catherine Wendy Spearman, Delawir Kahn, Malcolm Miller, Anthony Figaji, Eloy Erro, James Bundy, Isobel Massie, Sherri-Ann Chalmers, and Hiram Arendse "Evaluation of encapsulated liver cell spheroids in a fluidised-bed bioartificial liver for treatment of ischaemic acute liver failure in pigs in a translational setting." <i>PLoS One</i> (2013) http://hdl.handle.net/11427/15299 en_ZA
dc.identifier.vancouvercitation Selden C, Spearman CW, Kahn D, Miller M, Figaji A, Erro E, et al. Evaluation of encapsulated liver cell spheroids in a fluidised-bed bioartificial liver for treatment of ischaemic acute liver failure in pigs in a translational setting. PLoS One. 2013; http://hdl.handle.net/11427/15299. en_ZA
dc.identifier.ris TY - Journal Article AU - Selden, Clare AU - Spearman, Catherine Wendy AU - Kahn, Delawir AU - Miller, Malcolm AU - Figaji, Anthony AU - Erro, Eloy AU - Bundy, James AU - Massie, Isobel AU - Chalmers, Sherri-Ann AU - Arendse, Hiram AB - Liver failure is an increasing problem. Donor-organ shortage results in patients dying before receiving a transplant. Since the liver can regenerate, alternative therapies providing temporary liver-support are sought. A bioartificial-liver would temporarily substitute function in liver failure buying time for liver regeneration/organ-procurement. Our aim: to develop a prototype bioartificial-liver-machine (BAL) comprising a human liver-derived cell-line, cultured to phenotypic competence and deliverable in a clinical setting to sites distant from its preparation. The objective of this study was to determine whether its use would improve functional parameters of liver failure in pigs with acute liver failure, to provide proof-of-principle. HepG2cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4-6×10 10 cells, were transported from preparation-laboratory to point-of-use operating theatre (6000miles) under perfluorodecalin at ambient temperature. Irreversible ischaemic liver failure was induced in anaesthetised pigs, after portal-systemic-shunt, by hepatic-artery-ligation. Biochemical parameters, intracranial pressure, and functional-clotting were measured in animals connected in an extracorporeal bioartificial-liver circuit. Efficacy was demonstrated comparing outcomes between animals connected to a circuit containing alginate-encapsulated cells (Cell-bead BAL), and those connected to circuit containing alginate capsules without cells (Empty-bead BAL). Cells of the biomass met regulatory standards for sterility and provenance. All animals developed progressive liver-failure after ischaemia induction. Efficacy of BAL was demonstrated since animals connected to a functional biomass (+ cells) had significantly smaller rises in intracranial pressure, lower ammonia levels, more bilirubin conjugation, improved acidosis and clotting restoration compared to animals connected to the circuit without cells. In the +cell group, human proteins accumulated in pigs' plasma. Delivery of biomass using a short-term cold-chain enabled transport and use without loss of function over 3days. Thus, a fluidised-bed bioreactor containing alginate-encapsulated HepG2cell-spheroids improved important parameters of acute liver failure in pigs. The system can readily be up-scaled and transported to point-of-use justifying development at clinical scale. DA - 2013 DB - OpenUCT DO - 10.1371/journal.pone.0082312 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - Evaluation of encapsulated liver cell spheroids in a fluidised-bed bioartificial liver for treatment of ischaemic acute liver failure in pigs in a translational setting TI - Evaluation of encapsulated liver cell spheroids in a fluidised-bed bioartificial liver for treatment of ischaemic acute liver failure in pigs in a translational setting UR - http://hdl.handle.net/11427/15299 ER - en_ZA


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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Except where otherwise noted, this item's license is described as This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.