2D cell culture is still used around the world as a primary experimental tool, and with good reason. This traditional model has helped scientists identify toxicities associated with drug candidates, understand how viruses affect human cells, develop cancer treatments, and uncover many more medical marvels.
However, the lack of dimensionality and complexity of 2D models results in a less biologically relevant cell culture model. Without cells of the same type packed around them in three dimensions, and without cells of other types nearby, most human and animal cells simply don't develop the way they would in vivo.
3D Cell Culture Model Is Just Like the Real Thing
The differences in how 2D and 3D cell cultures behave are not minor in magnitude, nor are they random in nature. Complex biological processes almost always involve directional or density-based considerations that 2D cell cultures simply cannot account for. Tumor cells grown in 3D tissue culture can better replicate the gene expression patterns, heterogeneity in access to oxygen and nutrients, and drug responses found in solid tumors in vivo. Three-dimensional cultures of neural cells replicate aspects of cell-cell signaling and neural disease pathology that 2D cultures cannot provide.
Researchers have observed that 3D arrangements of tumor cells can affect cell behaviors, including differentiation, progression, and metastasis. Because these cells naturally exist in a 3D environment, they are almost always hardier and more viable in that form than in a thin layer or a monolayer. As a result, 2D cultures could systematically overestimate the effectiveness of chemical countermeasures.
Put simply, 3D cultures better mimic in vivo conditions because they naturally provide cells with a closer replica of the physical environment they need to interact with.