Synthetic tissue engineering: Programming multicellular self-organization by designing customized cell-cell communication.

Cells communicate with each other to organize multicellular collective systems and assemble complex, elaborate tissue structures by themselves during development. Despite intensive biological studies, what kind of cell-cell communication can sufficiently drive self-organization of specific tissue architectures remain unclear. Thanks to recent advances on genetic engineering technologies, synthetic biologists start to build customized cell-cell communication with user-defined signal input and gene expression output to program multicellular behaviors using mammalian systems. This review article introduces how we can design and engineer customized cell-cell communication to program synthetic self-organizing multicellular structures. Creating tissue formation processes with synthetic genetic programs will help understanding of fundamental principles of how genetic programs drive tissue self-organization and provide new capabilities on tissue engineering for cell-based regenerative therapy applications.