An evaluation of the replacement of animal-derived biomaterials in human primary cell culture
dc.contributor.author | Bramwell, LR | |
dc.contributor.author | Gould, SJ | |
dc.contributor.author | Davies, M | |
dc.contributor.author | McMullan, C | |
dc.contributor.author | Trusler, EC | |
dc.contributor.author | Harries, LW | |
dc.date.accessioned | 2024-08-14T09:34:34Z | |
dc.date.issued | 2024-08-09 | |
dc.date.updated | 2024-08-14T09:13:46Z | |
dc.description.abstract | The 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.sponsorship | Animal Free Research UK | en_GB |
dc.identifier.citation | Published online 9 August 2024 | en_GB |
dc.identifier.doi | https://doi.org/10.1177/02611929241269004 | |
dc.identifier.grantnumber | 18-001 | en_GB |
dc.identifier.grantnumber | 147 | en_GB |
dc.identifier.grantnumber | 149 | en_GB |
dc.identifier.grantnumber | 182 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/137158 | |
dc.language.iso | en | en_GB |
dc.publisher | SAGE Publications | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/39121342 | en_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.subject | animal component-free | en_GB |
dc.subject | animal-derived biomaterial | en_GB |
dc.subject | animal-free | en_GB |
dc.subject | cell culture | en_GB |
dc.subject | fetal bovine serum | en_GB |
dc.subject | human serum | en_GB |
dc.subject | humanisation | en_GB |
dc.subject | in vitro | en_GB |
dc.subject | tissue culture | en_GB |
dc.subject | xeno-free | en_GB |
dc.title | An evaluation of the replacement of animal-derived biomaterials in human primary cell culture | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2024-08-14T09:34:34Z | |
dc.identifier.issn | 0261-1929 | |
exeter.place-of-publication | England | |
dc.description | This is the final version. Available on open access from SAGE Publications via the DOI in this record. | en_GB |
dc.identifier.eissn | 2632-3559 | |
dc.identifier.journal | Alternatives to Laboratory Animals | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2024-08-09 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2024-08-14T09:28:04Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2024-08-14T09:34:47Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2024-08-09 |
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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).