The Development and Applications of Novel Bioengineered Human Epithelial Tissue Models and the Role of Tissue-Specific Fibroblasts

Abstract

Epithelial tissues are critical for survival as they represent the first line of defence between the body and the external environment. Arising from all three germ layers, epithelia are a diverse group of tissues which line the internal cavities and cover most of the body and organ surfaces. Therefore, there is a high demand for epithelial tissues for research and testing purposes. However, supply is limited, and most epithelia-based studies rely upon simplistic 2D cultures and animal models which are subject to a number of limitations including variability, major ethical considerations and difficulties in relating findings back to humans due to structural and functional differences.

Epithelial tissues share a common, highly conserved structure comprising a surface epithelium which is supported by an underlying basement membrane and fibroblast- populated connective tissue compartment. However, the importance and complexity of this subepithelial compartment is often overlooked.

The advent of advanced 3D cell culture technologies and tissue engineering techniques has enabled the development of tissue-like constructs in vitro. Utilising a bottom up approach whereby human fibroblasts seeded into Alvetex® Scaffold are able to deposit endogenous extracellular matrix components and generate a dynamic stromal environment, we have successfully generated a range of novel bioengineered epithelial tissue models. Through extensive characterisation, we have shown that our respective tissue models demonstrate structural morphology resembling the architecture of native human skin, oral and nasal mucosa. Due to the fundamental anatomical principle that structure is related to function, the ability of these models to mimic the structure and thus function of their in vivo counterparts is critical to their success.

We hypothesise that signalling from fibroblasts within the subepithelial compartment is critical to the differentiation of the overlying epithelium and propose that these tissue engineered models provide valuable platforms for a range of both industrial and academic applications.