Is It Time to Start Transitioning From 2D to 3D Cell Culture?

Abstract

Cell culture is an important and necessary process in drug discovery, cancer research, as well as stem cell study. Most cells are currently cultured using two-dimensional (2D) methods but new and improved methods that implement three-dimensional (3D) cell culturing techniques suggest compelling evidence that much more advanced experiments can be performed yielding valuable insights. When performing 3D cell culture experiments, the cell environment can be manipulated to mimic that of a cell in vivo and provide more accurate data about cell-to-cell interactions, tumor characteristics, drug discovery, metabolic profiling, stem cell research, and other types of diseases. Scaffold based techniques such as hydrogel-based support, polymeric hard material-based support, hydrophilic glass fiber, and organoids are employed, and each provide their own advantages and applications. Likewise, there are also scaffold free techniques used such as hanging drop microplates, magnetic levitation, and spheroid microplates with ultra-low attachment coating. 3D cell culture has the potential to provide alternative ways to study organ behavior via the use of organoids and is expected to eventually bridge the gap between 2D cell culture and animal models. The present review compares 2D cell culture to 3D cell culture, provides the details surrounding the different 3D culture techniques, as well as focuses on the present and future applications of 3D cell culture.

Keywords: 3D cell culture; advance and progress; biomedical and drug research; methods and applications; techniques.

FIGURE 1

Number of publications per year (1968–2020) on 3D cell cultures gathered from PubMed.

FIGURE 2

Representative images of cancer cells growing in the SeedEZ scaffold, a new 3D culture system with transparent glass microfibers. Head and neck cancer HN17 cells expressing green fluorescent protein (GFP) were seeded in SeedEZ for 7 days, and images were taken under a fluorescence microscope.