Methods for Engineering of Multicellular Spheroids to Reconstitute the Liver Tissue

Abstract Multicellular spheroid (MCS) culture has been believed to mimic three-dimensional environments in our body. For instance, hepatocytes show higher functions in the MCS condition. The inner structure of the MCS is, however, not well organized, and engineering of the configuration would be effective to represent further liver characteristics. This chapter will show how to reconstruct the liver-like tissues in vitro by the engineering of MCS those are based on a swelling phenomenon of a culture medium dissolving polymer molecule. The unique method enables us to engineer the microarchitectures in the MCS by formation of void spaces or filling of extracellular matrices. The liver functions/features are enhanced/improved by regulating microenvironment. Fabrication of the MCS with microstructures would achieve a breakthrough in study for stem cells and cancer, animal testing alternative, human-on-a-chip, and regenerative medicine.