Three-dimensional tissue cultures: current trends and beyond

Abstract

Life science research focuses on deciphering the biochemical mechanisms that regulate cell proliferation and function and largely depends on the use of tissue culture methods in which cells are grown on two-dimensional hard plastic or glass surfaces. However, the flat surface of the tissue culture plate represents a poor topological approximation of the complex three-dimensional (3D) architecture of a tissue or organ composed of various cell types, extracellular matrix (ECM) and interstitial fluids. Moreover, if we consider a cell as a perfectly defined volume, flattened cells have full access to the environment and limited cell-to-cell contact. However if the cell is a cube in a simple cuboidal epithelium, then its access to the lumen is limited to one face, with the opposite face facing the basal membrane and the remaining four faces lying in close contact with neighbouring cells. This is of great importance when considering the access of viruses and bacteria to the cell surface, the excretion of soluble factors or proteins or the signalling within or between cells. This short review discusses various cell culture approaches to improve the simulation of the 3D environment of cells.

Cell-to-cell communication: current views and future perspectives

“…Page et al (2012) discuss, in their review, 3D cell culture approaches currently used to mimic a tissue-like environment. These include multicellular spheroids produced by various methods and 3D scaffold-based systems composed of synthetic or naturally derived biomaterials that simulate the extracellular matrix of tissue.…”

Invited Review Article: Advanced light microscopy for biological space research

“…Different approaches with varying complexity exist to generating three-dimensional cell cultures, several of which make use of feeder layers, collagen matrices, or other scaffolds. 36 The simplest, yet powerful alternative is the use of cellular spheroids, which do not require external scaffolds and can be obtained from many different cell types by seeding cells in hanging drops or on non-adhesive cellrepellent) surfaces. They can also be generated by employing tools that simulate μg such as random positioning machines or rotating wall vessels.…”

Quantification of substrate and cellular strains in stretchable 3D cell cultures: an experimental and computational framework

“…In comparison to traditional 2D cell culture systems, 3D culture mimics structural, dimensional and mechanical properties of tissue (Page et al, 2013) and allows a more physiological arrangement of cellular structures.…”