When looking to answer complex biological questions, using in vitro techniques, you want the model that best reflects the in vivo condition.  For decades two-dimensional cell culture has dominated in this regard.  However, is it accurate to equate flat two-dimensional growing single monolayer cells to a complex three-dimensional tissue or organ system? Organs boast a unique three-dimensional cellular architecture, with cell-cell and cell-matrix interactions, creating a complex communication network through biochemical and mechanical signals.  However, important and distinct differences exist between 2D and 3D cell culturing, as well as the in vivo situation.  Differences between these two culturing extremes culminate into discrepancies in treatment responses.  Proof of concept suggests that 3D models may be more apt at providing information when evaluating new lead compounds.  Various types of 3D cell culture model systems are currently available and being explored.  The choice of system depends on the hypothesis, study design or target organ, and not one system is superior to the other with each offering various advantages and disadvantages.  The dynamic micro-gravity spheroid 3D system exhibits the ability to overcome many of the shortcomings of traditional 2D cell cultures.  In implementing this system in our laboratories, findings obtained from 2D and 3D in vitro hepatoxicity experiments showed significant discrepancies between the two systems.  While 3D experiments compared to an in vivo animal model, indicated that the 3D model is able to accurately predict possible hepatoxic events.  Looking at all the information provided, I put it to you, does dimension really matter?

Learning Objectives: 

1. What are the major differences between two-dimensional and three-dimensional cell culture, and how will this influence results.
2. The potential applications of novel three-dimensional cell culture models and techniques in cell biology.