Wnt signaling activation for regeneration of inner ear hair cell

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1.Knockout of GSK-36Wnt signaling is the important signal transduction pathway for cell proliferation. Beta-catenin stabilized mouse was used as experimental animal. Using adenovirus vector and Cre-loxP system in the culture preparation of organ of Corti at various conditions, we tried to knock out GSK-36; a inhibiting factor of Wnt signaling.2.Pharmacological inhibition of GSK-36In the culture preparation of organ of Corti, GSK-36 was blocked by several drugs, such as Kenpaullone Indirubin-3'-monoxime. GSK-3 Inhibitor II, BIO and so on. In some specimens, hair cells seemed to be proliferated.3.In vivo experiments on activation of Wnt signalingFollowing in vitro experiments, in vivo regeneration of inner ear hair cells has been tried by activating of Wnt signal through round window for future clinical application. Two types of administration devices, continuous infusion pump and biodegradable hydrogel, have been used. However, proliferation and regeneration of inner ear hair cells have not been observed yet.