Aqueous two-phase emulsion systems in 3D cell culture

The development of realistic 3D cell culture models by using emulsions and capillary suspensions based on aqueous two-phase systems (ATPS) has advanced the areas of cell physiology and biology. It has shown the potential to enhance the fields of cancer research, biotechnology, rapid testing of drug efficiency and toxicity, tissue engineering, as well as regenerative medicine. It has been increasingly accepted that 3D cells culture more closely reflects normal cellular function due to the enhanced cell interactions, which mimic the in vitro microenvironment and architecture of natural organs and tissues. In this review, we discuss the ATPS-aided methods to form 3D cell spheroids and cell networks by using colloids as templates for the purposes of cell structuring and will discuss the limitations and the advantages of these approaches. The use of ATPS-based cell spheroids has helped to advance basic cell sciences, including understanding cancer cell interactions with their environment in solid tumors, creating better drug models and studying cancer metastasis. Such multi-cellular assemblies have also been applied for engineering tissue constructs which have great potential for studying cell interactions in biological systems under a more realistic in vitro environment compared to 2D cell culture.