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.authorSelden, Clareen_ZA
dc.contributor.authorSpearman, Catherine Wendyen_ZA
dc.contributor.authorKahn, Delawiren_ZA
dc.contributor.authorMiller, Malcolmen_ZA
dc.contributor.authorFigaji, Anthonyen_ZA
dc.contributor.authorErro, Eloyen_ZA
dc.contributor.authorBundy, Jamesen_ZA
dc.contributor.authorMassie, Isobelen_ZA
dc.contributor.authorChalmers, Sherri-Annen_ZA
dc.contributor.authorArendse, Hiramen_ZA
dc.date.accessioned2015-11-23T12:29:40Z
dc.date.available2015-11-23T12:29:40Z
dc.date.issued2013en_ZA
dc.description.abstractLiver 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.identifier.apacitationSelden, 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/11427/15299en_ZA
dc.identifier.chicagocitationSelden, 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/11427/15299en_ZA
dc.identifier.citationSelden, 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.0082312en_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
dc.identifier.urihttp://hdl.handle.net/11427/15299
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0082312
dc.identifier.vancouvercitationSelden 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.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Hepatologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis 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.holder© 2013 Selden et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherAcute liver failureen_ZA
dc.subject.otherSwineen_ZA
dc.subject.otherBlood plasmaen_ZA
dc.subject.otherLiver transplantationen_ZA
dc.subject.otherAlbuminsen_ZA
dc.subject.otherAmmoniaen_ZA
dc.subject.otherIschemiaen_ZA
dc.subject.otherBilirubinen_ZA
dc.titleEvaluation of encapsulated liver cell spheroids in a fluidised-bed bioartificial liver for treatment of ischaemic acute liver failure in pigs in a translational settingen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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