Cell culture consists in growing cells in an artificial environment in order to study their behavior in response to their environment. Different kinds of cell cultures can be found nowadays, and some would be more suited than others depending on its properties and applications.
Amongst them, 3D cell culture has been increasingly used for its new and convenient features compared to other alternative cell culture method. 3D cell culture could be described as the culture of living cells within micro-assembled devices and supports that present a three dimensional structures mimicking tissue and organ specific microarchitecture. In literature, there are some commendable reviews tackling 3D cell culture in-depth such as John W. Haycock et al. “3D Cell Culture: A Review of Current Approaches and Techniques”, and this review mostly relies on those excellent references.
2D cell culture has traditionally been used over the past decades not only to study different cellular types in vitro but also to conduct drug screening and testing. Typically, this monolayer system allows cell growth over a polyester or glass flat surface presenting a medium that feeds the growing cell population. Countless biological breakthroughs occurred thanks to 2D cell culture. However due to its simplicity, this model can’t accurately depict and simulate the rich environment and complex processes observed in vivo such as cell signaling, chemistry or geometry. Consequently, data gathered with 2D cell culture methods could be misleading and non-predictive for in vivo applications. That’s the reason why scientists have recently been working on three-dimensional biomimetic cell cultures, a technique that represents more precisely the actual microenvironment in which cells can thrive in vivo.
As you may already be aware of, there are different type of 3D cell culture, with each kind of them offering different avantages and drawbacks. Unlike 2D cell culture, 3D cell culture facilitate cell differentiation and tissue organization by using micro-assembled structures and a complex environmental parameters. In fact, in a 3D environment, cells tend to be more subjected to morphological and physiological changes contrary to those grown in a 2D environment. This can mostly be explain by the structuring role and the influence of the scaffold that guide the cells behavior. Researchers have found that the geometry and composition of this cellular support can not only influence genes expression but also enhance cell-cell communication. For instance, some genes promoting cell proliferation are repressed in a 3D cell culture, hence avoiding the anarchic proliferation encountered in 2D cell cultures.
3D cell culture also grants the possibility to grow simultaneously two different cellular populations with co-cultures accurately reproducing cellular functions observed within a tissue unlike co-cultures based on 2D cell culture. Interactions existing between cells of interest and others cell are obviously key element in cell functions. That’s the reason why studies focusing on stromal cell (organ connective cell tissues) that play an important part in cancer have been conducted. Finally, using 3D cell culture make it easier to control and monitor the growing cells micro-environment parameters (temperature, chemical gradients, oxygen rate, pH, etc.) to a certain extent while remaining as close to reality as possible thanks to micro-engineering (microfluidic).
One must bear in mind that 3D cell culture is a relatively new technique that researchers have not yet fully grasped the underlying phenomenon and implications. Unfortunately, this culture method presents some noticeable downsides that would most likely be overcome by technological advances. First, some scaffold matrices incorporate compounds from animal or others unwanted sources (virus, soluble factors) that could interfere with the cell culture. Some other matrices provide good cell adherence, making cell removal all the more difficult. Beside, while 3D cell culture could be a cost saving technique that would skip the animal drug testing step in drugs trials, developing automation and reproducible applications still remains a very costly and meticulous process.