In vitro morphological bud formation in organ-like three-dimensional structure from mouse ES cells induced by FGF10 signaling

Embryonic stem (ES) cells have a pluripotent ability to differentiate into a variety of cell lineages in vitro. Using an embryoid body (EB) culture system, we developed a gut-like three-dimensional structure from mouse ES cells (the ES 3-D structure). Genetic studies implicate fibroblast growth factor 10 (FGF10)-FGF receptor 2b (FGFR2b) signaling as a critical regulator of lung bud morphogenesis in the embryonic foregut. The aim of the present study was to form a putative respiratory tract in the ES 3-D structure. By local application of FGF10 protein, we successfully demonstrated in vitro morphological formation of putative primitive respiratory tract-like processes, or buds, in the ES 3-D structure. Such organs that are differentiated from ES cells may provide new insights into tissue engineering and regenerative medicine.