The third dimension: new developments in cell culture models for colorectal research

Cellular models are important tools in various research areas related to colorectal biology and associated diseases. Herein, we review the most widely used cell lines and the different techniques to grow them, either as cell monolayer, polarized two-dimensional epithelia on membrane filters, or as three-dimensional spheres in scaffoldfree or matrix-supported culture conditions. Moreover, recent developments, such as gut-on-chip devices or the ex vivo growth of biopsy-derived organoids, are also discussed. We provide an overview on the potential applications but also on the limitations for each of these techniques, while evaluating their contribution to provide more reliable cellular models for research, diagnostic testing, or pharmacological validation related to colon physiology and pathophysiology.

Work in the authors’ laboratories is supported by Fundação para a Ciência e Tecnologia (FCT) through center Grant UID/MULTI/04046/2013 (to BioISI), by research grants from FCT, Portugal (PTDC/BIM-MEC/2131/2014), CFF-Cystic Fibrosis Foundation, USA (AMARAL15XX0, AMARAL15XX1), Gilead GÉNESE-Portugal Programme (PGG/008/2015); CF Trust, UK (SRC 003) to MDA, and from Portuguese association for inflammatory bowel disease (GEDII 2013), Portuguese association Maratona da Saúde (Cancro 2014), Portugal to PJ. J.F.P. was supported by fellowships BRJ-DGH 2012_oncologia from Instituto Nacional de Saúde Doutor Ricardo Jorge (Lisbon, Portugal) and BD/109162/2015 from FCT.