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dc.contributor.authorBramwell, LR
dc.contributor.authorGould, SJ
dc.contributor.authorDavies, M
dc.contributor.authorMcMullan, C
dc.contributor.authorTrusler, EC
dc.contributor.authorHarries, LW
dc.date.accessioned2024-08-14T09:34:34Z
dc.date.issued2024-08-09
dc.date.updated2024-08-14T09:13:46Z
dc.description.abstractThe likelihood that potential new drugs will successfully navigate the current translational pipeline is poor, with fewer than 10% of drug candidates making this transition successfully, even after their entry into clinical trials. Prior to this stage, candidate drugs are typically evaluated by using models of increasing complexity, beginning with basic in vitro cell culture studies and progressing through to animal studies, where many of these candidates are lost due to lack of efficacy or toxicology concerns. There are many reasons for this poor translation, but interspecies differences in functional and physiological parameters undoubtedly contribute to the problem. Improving the human-relevance of early preclinical in vitro models may help translatability, especially when targeting more nuanced species-specific cell processes. The aim of the current study was to define a set of guidelines for the effective transition of human primary cells of multiple lineages to more physiologically relevant, translatable, animal-free in vitro culture conditions. Animal-derived biomaterials (ADBs) were systematically replaced with non-animal-derived alternatives in the in vitro cell culture systems, and the impact of the substitutions subsequently assessed by comparing the kinetics and phenotypes of the cultured cells. ADBs were successfully eliminated from primary human dermal fibroblast, uterine fibroblast, pulmonary fibroblast, retinal endothelial cell and peripheral blood mononuclear cell culture systems, and the individual requirements of each cell subtype were defined to ensure the successful transition toward growth under animal-free culture conditions. We demonstrate that it is possible to transition ('humanise') a diverse set of human primary cell types by following a set of simple overarching principles that inform the selection, and guide the evaluation of new, improved, human-relevant in vitro culture conditions.en_GB
dc.description.sponsorshipAnimal Free Research UKen_GB
dc.identifier.citationPublished online 9 August 2024en_GB
dc.identifier.doihttps://doi.org/10.1177/02611929241269004
dc.identifier.grantnumber18-001en_GB
dc.identifier.grantnumber147en_GB
dc.identifier.grantnumber149en_GB
dc.identifier.grantnumber182en_GB
dc.identifier.urihttp://hdl.handle.net/10871/137158
dc.language.isoenen_GB
dc.publisherSAGE Publicationsen_GB
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pubmed/39121342en_GB
dc.rights© The Author(s) 2024. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).en_GB
dc.subjectanimal component-freeen_GB
dc.subjectanimal-derived biomaterialen_GB
dc.subjectanimal-freeen_GB
dc.subjectcell cultureen_GB
dc.subjectfetal bovine serumen_GB
dc.subjecthuman serumen_GB
dc.subjecthumanisationen_GB
dc.subjectin vitroen_GB
dc.subjecttissue cultureen_GB
dc.subjectxeno-freeen_GB
dc.titleAn evaluation of the replacement of animal-derived biomaterials in human primary cell cultureen_GB
dc.typeArticleen_GB
dc.date.available2024-08-14T09:34:34Z
dc.identifier.issn0261-1929
exeter.place-of-publicationEngland
dc.descriptionThis is the final version. Available on open access from SAGE Publications via the DOI in this record. en_GB
dc.identifier.eissn2632-3559
dc.identifier.journalAlternatives to Laboratory Animalsen_GB
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_GB
rioxxterms.versionVoRen_GB
rioxxterms.licenseref.startdate2024-08-09
rioxxterms.typeJournal Article/Reviewen_GB
refterms.dateFCD2024-08-14T09:28:04Z
refterms.versionFCDVoR
refterms.dateFOA2024-08-14T09:34:47Z
refterms.panelAen_GB
refterms.dateFirstOnline2024-08-09


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© The Author(s) 2024. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
Except where otherwise noted, this item's licence is described as © The Author(s) 2024. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).