STUDY ON HAIR CELL REGENERATION IN THE MAMMALIAN COCHLEA

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1)We examined the types of cells that can be tranfected with adenovirus vector. We injected an Adex1CAlacZ into the guinea pig cochlear or vestibular explants. We found expression of lacZ in a variety of cochlear tissues including the spiral ganglion, stria vascularis, and the outer hair cells and supporting cells. In the vestibular labyrinth, the mesothelial cells in the perilymphatic space, the sensory and supporting cells in the utricle and ampulla and the transitional and dark cells in the ampulla were transfected. In vivo, we found that damage from a local anesthetic solution containing phenol permitted LacZ gene delivery to the guinea pig inner ear via the round window membrane.2)We investigated the effects of dexamethasone-induced immunosuppression on the outcome of adenovirus gene transfer in guinea pig inner ears and found that immunosuppressive treatment reduced the negative consequences of repeated adenovirus-mediated gene therapy.3) We demonstrate that in vivo inoculation of adenovirus with the Math 1 gene insert into the mature guinea pig cochlea results in Math 1 overexpression in nonsensory cochlear cells. Math 1 overexpression leads to the appearance of immature hair cells in the organ of Corti and new hair cells adjacent to the organ of Corti in the interdental cell, inner sulcus, and Hensen cell regions. Axons are extended from the bundle of auditory nerve toward some of the new hair cells, suggesting that the new cells attract auditory neurons.4)We assessed mitotic activity in the auditory sensory epithelium throughout the mature cochlea of deafened guinea pigs given BrdU for up to 10 days. We found BrdU-positive cells within the organ of Corti from 3 to 30 days following deafening. Immunohistochemistry confirmed that the BrdU-positive cells were the Deiters cells, These findings indicate that, albeit limited, the Deiters cells in the mature mammalian cochlea possess a potential of mitotic activity and that they could survive after mitosis.