Modeling Physiological Events in 2D vs. 3D Cell Culture

Abstract

Cell culture has become an indispensable tool to help uncover fundamental biophysical and biomolecular mechanisms by which cells assemble into tissues and organs, how these tissues function, and how that function becomes disrupted in disease. Cell culture is now widely used in biomedical research, tissue engineering, regenerative medicine, and industrial practices. Although flat, two-dimensional (2D) cell culture has predominated, recent research has shifted toward culture using three-dimensional (3D) structures, and more realistic biochemical and biomechanical microenvironments. Nevertheless, in 3D cell culture, many challenges remain, including the tissue-tissue interface, the mechanical microenvironment, and the spatiotemporal distributions of oxygen, nutrients, and metabolic wastes. Here, we review 2D and 3D cell culture methods, discuss advantages and limitations of these techniques in modeling physiologically and pathologically relevant processes, and suggest directions for future research.

FIGURE 1.

Three different applications and variations of cell sheet engineering A: a cornea transplant using a single cell sheet. B: layered identical cell sheets for myocardial reconstruction. C: layers of various cell sheet types for liver or kidney applications. Reprinted from Ref. , with permission from Biomaterials.

FIGURE 2.

A lung-on-a-chip created by culturing human alveolar epithelial cells and pulmonary microvascular endothelial cells A: a lung-on-a-chip created by culturing human alveolar epithelial cells and pulmonary microvascular endothelial cells on opposing sides of a porous membrane. B: the system could recreate organ-level functions, such as an inflammatory response bacteria. C: the system was also used as a model for lung diseases like pulmonary edema. Reprinted from Ref. , with permission from Nature Reviews Drug Discovery.

FIGURE 3.

Cells in 2D and 3D microenvironments interact differently with their surroundings due to differences in the cues, mechanical and chemical, that they experience Reprinted from Ref. , with permission from Journal of Cell Science.