A Preclinical Model of Human Liver Using Precision Cut Tissue Slice Culture

Preclinical models vary in complexity and cost. Traditional 2D cell cultures that are high throughput and cost effective, but lack the complexity of multicellular interactions. Animal models and more complex, but are costly, raise ethical concerns and are not a human model to better understand human disease or response to novel treatments. Human precision cut tissue slice (hPCTS) models bridge this gap, maintaining the architecture and microenvironment of original tissues. This study examines the viability and functionality of hPCTS using different tissue culture formats. Previous studies have cultured hPCTS with gentle agitation, either on an insert or floating in tissue culture medium. More recently the use of a proprietary flow system for hPCTS culture has been explored, aiming to provide a more physiologically relevant environment. CELLBLOKS® provide a commercially available flow system platform designed for cell culture that we adapted to accommodate hPCTS. hPCTS were cultured for 15 days using an organotypic polytetrafluoroethylene Millicell insert, a CELLBLOKS® hydrophilic polyethylene terephthalate flow system plate or without an insert. Viability was assessed through MTS assays, while functionality was determined by measuring urea and albumin secretion across the 15 days in culture. The Millicell inserts maintained higher and more consistent viability and functionality over 15 days. Slices cultured with no inserts showed decreased viability and functionality after 7 days in culture. In contrast, CELLBLOKS® cultured hPCTS showed significantly decreased viability and function after 3 days in culture. This study suggests that while the CELLBLOKS® system shows promise for 2D cell line cultures, Millicell Biopore™ inserts offer a more reliable method for maintaining complex hPCTS cultures, preserving both viability and function. As a viable, human-specific alternative to animal models, hPCTS support the 3Rs and have the potential to reduced and potentially replace the use of animals in preclinical research, improving human disease modelling.