Differentiation of iPS Cells toCochlear Cells are RegulatedDepending on the Part of CoculturedOrgans

Background: Induced pluripotent stem (iPS) cells aremultipotentstem cellsthat can be producedfrom adult cells such as fibroblastsby the induction ofartificial reprogramming.Since such cells can be differentiated to endoderm, mesodermand ectoderm asembryonic stem (ES) cells, theirpotential utility for the regenerative therapy of various organs is expected. The inner ear is composed of various types of functional cells (hair cells, supporting cells, spiral ganglion, cochlear fibrocytes, striavascularis, etc.), and each cell type. Although the degeneration of these cells leads directly to severe hearing loss, there are few reports concerning thedifferentiation of iPS cells to various types of inner ear cells for regenerative therapy.Results: In this study, we co-cultured iPS-derived cells with three different regions (spiral ganglion, the organ of Corti with spiral limbus, lateral wall) of the cochlear tissue and tod attempted to induce their differentiation into various types of inner ear cells. The number of positive colonies (Nanogpositive colony) with reporter GFP controlled by Nanogpromotor was counted to assess the undifferentiated level of the cells. In the co-cultured cells with spiral ganglion, many Nanog-positive colonies were observed, and many cells with neurite-like protrusions were observed among the colonies. In the co-culture with the organ of Cortiand spiral limbus (OC/SL), neuron-like cells were observed on the cell layer with tight junction-like adhesions. In the co-culture with the cochlear lateral wall, many cell layers with tight junction-like adhesions were observed, while undifferentiated Nanogpositive colonies were not observed. Conclusion: In this study, we demonstrated that differentiation of iPS cells to cochlear cells was regulated depending on the part of the co-cultured organs. Co-culture with cochlea tissue and the induced pluripotent stem cells may enable regenerative therapy of various types of inner ear cells.