A review of co-culture models to study the oral microenvironment and disease

Abstract

Co-cultures allow for the study of cell-cell interactions between different eukaryotic species or with bacteria. Such an approach has enabled researchers to more closely mimic complex tissue structures. This review is focused on co-culture systems modelling the oral cavity, which have been used to evaluate this unique cellular environment and understand disease progression. Over time, these systems have developed significantly from simple 2D eukaryotic cultures and planktonic bacteria to more complex 3D tissue engineered structures and biofilms. Careful selection and design of the co-culture along with critical parameters, such as seeding density and choice of analysis method, have resulted in several advances. This review provides a comparison of existing co-culture systems for the oral environment, with emphasis on progression of 3D models and the opportunity to harness techniques from other fields to improve current methods. While filling a gap in navigating this literature, this review ultimately supports the development of this vital technique in the field of oral biology.

Keywords: 3D-in vitro models; Co-culture; NC3Rs; biofilms; oral cavity; oral disease.

Figure 1.

(a) Common bacterial species present in pathogenic oral biofilms and their communication between species (adapted from Parashar et al. [92]). (b) Cells and tissue types present in the oral mucosa, demonstrating complexity of 3D structure.

Figure 2.

Common co-culture systems reported in the literature (a) monospecies 2D cell culture with planktonic bacteria applied; (b) multispecies 2D cell culture with planktonic bacteria applied; (c) multispecies 3D cell culture, typically a collagen-based or decellularised matrix containing fibroblasts, with planktonic bacteria applied; and (d) monospecies 2D cell culture with biofilm applied, typically suspended from a well insert.