In recent years, researchers have attempted to provoke the regeneration of lost sensory hair cells in the inner ear, a potential treatment for forms of deafness. Various genes related to the creation of these cells during development have been identified, and gene therapy interventions attempted in animal models. Progress has been made, but it is incremental, and the results not yet satisfactory. Noted here is a recent example of this sort of work, in which a cocktail of genes is employed rather than focusing on single gene interventions.
The transcription factors (genes) Gfi1, Atoh1, Pou4f3, and Six1 (known collectively as GAPS) are important for the development and survival of hair cells. Previous research trying to regenerate hair cells in mature damaged ears by using a single transcription factor, Atoh1, produced very few cells. It also failed to produce new hair cells in severely injured organs of Corti, especially those with flat epithelium, a condition where sensory hair cells and supporting cells in the cochlea are lost and the organ of Corti turns into a simple flat layer of cells.
Studies in vitro suggested using combinations of transcription factors could be more effective than any single factor. We looked at the effects of overexpressing the GAPS genes in the ears of mature guinea pigs that were deafened and had flat epithelium. Seven days after deafening, adenovirus vectors carrying GAPS were injected into the inner ear scala media (cochlear duct) and successfully expressed in the flat epithelium. One or two months later, we observed cells expressing the protein Myosin VIIa, which marks hair cells. Surprisingly, most of these cells were in regions under the flat epithelium, not within it. Two months after treatment, we saw that some GAPS-treated guinea pigs had a statistically significant increase in new hair cell-like cells compared with controls.
In summary, our results showed that overexpression of GAPS enhances the potential for generating new hair cell-like cells in a severe inner ear lesion model characterized by flat epithelium in the guinea pig, compared with using Atoh1 alone. The new hair cells need to connect with nerve fibers to potentially restore hearing. We saw some promising signs of nerve regrowth, but more research is needed to determine if the new cells can signal to auditory nerves, even in their unusual location.
Link: https://hearinghealt...ells-in-mammals
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