The cellular microenvironment in vivo and in vitro. (A) In the body, cells exist in a complex microenvironment surrounded by a wide range of stimuli (an example of an epithelial tissue is shown). These include mechanical stimulation such as from blood flow, contact between a large number of cells, both of the same type and different types, and contact with structural support such as the extracellular matrix and basement membranes. (B) Many of these factors are missing in standard in vitro monolayer culture. The lack of a 3D growth surface leads cells to flatten out, minimising contact with other cells. Cells adhere to the growth surface in a single direction, leading to an enforced polarisation which may not resemble that found in vivo.