Mimicking Epithelial Tissues in Three-Dimensional Cell Culture Models

Abstract

Epithelial tissues are composed of layers of tightly connected cells shaped into complex three-dimensional (3D) structures such as cysts, tubules, or invaginations. These complex 3D structures are important for organ-specific functions and often create biochemical gradients that guide cell positioning and compartmentalization within the organ. One of the main functions of epithelia is to act as physical barriers that protect the underlying tissues from external insults. In vitro, epithelial barriers are usually mimicked by oversimplified models based on cell lines grown as monolayers on flat surfaces. While useful to answer certain questions, these models cannot fully capture the in vivo organ physiology and often yield poor predictions. In order to progress further in basic and translational research, disease modeling, drug discovery, and regenerative medicine, it is essential to advance the development of new in vitro predictive models of epithelial tissues that are capable of representing the in vivo-like structures and organ functionality more accurately. Here, we review current strategies for obtaining biomimetic systems in the form of advanced in vitro models that allow for more reliable and safer preclinical tests. The current state of the art and potential applications of self-organized cell-based systems, organ-on-a-chip devices that incorporate sensors and monitoring capabilities, as well as microfabrication techniques including bioprinting and photolithography, are discussed. These techniques could be combined to help provide highly predictive drug tests for patient-specific conditions in the near future.

A three-dimensional intestinal tissue model reveals factors and small regulatory RNAs important for colonization with Campylobacter jejuni

“…Among 3D cell culture approaches [31,32], tissue engineering combines the support of scaffolds with the appropriate mammalian cell type to create in-vitro engineered complex 3D tissue models harboring the microarchitecture of human organs [33]. To develop such an infection model for C. jejuni infection studies, we built on a previously established tissue-engineered model for the small intestine, in which human Caco-2 cells are reseeded on the extracellular matrix scaffold SISmuc (Small Intestinal Submucosa) [34][35][36].…”

Imaging the Cell Morphological Response to 3D Topography and Curvature in Engineered Intestinal Tissues

“…Many epithelial tissues exhibit complex morphologies that are mostly dominated by curved surfaces such as those found in lung alveoli and intestinal villi (Torras et al, 2018;Baptista et al, 2019). These three-dimensional (3D) topographies generate gradients in biochemical signals and mechanical tension that play a key role in cell polarization, morphology, and function (Farin et al, 2016;Krndija et al, 2019).…”

Organ-on-a-chip: recent breakthroughs and future prospects

“…OOAC technology has developed rapidly in recent years and has enhanced our knowledge of all the major organs. Others not discussed in this review include blood vessels [99,114,115], the skin [116,117], the BBB [118,119], skeletal muscle [120,121], and the CNS [122,123].…”