An evaluation of the replacement of animal-derived biomaterials in human primary tissue culture

Abstract

Abstract The ability of newly developed drugs to navigate the current translational pipeline is extremely poor, with less than 10% of drugs making this transition even after entry into clinical trials. There are many reasons for this, but interspecies differences in functional and physiological parameters contribute to the problem. Improving the humanrelevance of early pre-clinical in vitro models may help translatability, especially when targeting more nuanced species-specific cell processes. We aimed to define a set of guidelines for effective transition of human primary cells of multiple lineages into a more physiologically relevant, translatable, animal-free culture environment by systematic replacement of animal-derived biomaterials in in vitro culture systems, followed by assessment of effects on cell kinetics and phenotype. We successfully eliminated animalderived biomaterial from primary human dermal fibroblast, uterine fibroblast, pulmonary fibroblast, retinal endothelial cell, and peripheral blood mononuclear cell culture systems and defined the individual requirements of each cell subtype for transition to animal-component free culture conditions. We therefore demonstrate that it is possible to transition (“humanise”) a diverse set of human primary cell types by following a set of simple overarching principals that inform the selection, and guide the evaluation of new, improved, human-relevant culture conditions.