Engineering of three-dimensional liver micro-tissue containing sinusoidal ultrastructure through heterotypic cell-cell interactions

We developed the vascularized 3D liver-mimic micro-tissue including sinusoids and fenestrated endothelium consists of three types of liver cells by tri-culturing them on concave microwells depending on their spontaneous heterotypic interactions. The tri-cultured spheroids maintained long-term viability and functions in vitro, and showed a sinusoidal ultrastructure, allowing toxins to be secreted and supporting long life. Using this model, we also made some physiological discoveries about heterotypic interactions and fibrosis. This is the most in vivo-like liver model reported to date, and the first report about the micro-tissue containing three primary liver cells in 3D structure and having liverspecific inner structures.