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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
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, Volume 8, No. 12, Article e82312, Year 2013
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Description
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 4-6×1010 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. © 2013 Selden et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3867376/bin/pone.0082312.s001.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3867376/bin/pone.0082312.s002.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3867376/bin/pone.0082312.s003.tif
Authors & Co-Authors
Selden, Clare A.
United Kingdom, London
Ucl Medical School
Spearman, W. C.
South Africa, Observatory
Groote Schuur Hospital
Kahn, Delawir H.
South Africa, Observatory
Groote Schuur Hospital
Miller, Malcolm G.A.
South Africa, Observatory
Groote Schuur Hospital
Figaji, Anthony A.
South Africa, Cape Town
University of Cape Town
Erro, Eloy
United Kingdom, London
Ucl Medical School
Bundy, James
United Kingdom, London
Ucl Medical School
Massie, Isobel
United Kingdom, London
Ucl Medical School
Chalmers, Sherri Ann
United Kingdom, London
Ucl Medical School
Arendse, Hiram
South Africa, Observatory
Groote Schuur Hospital
Gautier, Aude
United Kingdom, London
Ucl Medical School
Sharratt, Peter
United Kingdom, Cambridge
University of Cambridge
Fuller, Barry J.
United Kingdom, London
Ucl Medical School
Hodgson, Humphrey J.F.
United Kingdom, London
Ucl Medical School
Statistics
Citations: 41
Authors: 14
Affiliations: 4
Identifiers
Doi:
10.1371/journal.pone.0082312
e-ISSN:
19326203