1. AAV-regulated Serpine2 overexpression promotes hair cell regeneration.
- Author
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Sun, Q., Zhou, Y., Tan, F., Gu, X., Li, N., Zhang, Z., Lu, Y., Wang, M., Zhang, L., Tong, B., Qi, J., and Chai, R.
- Subjects
TREATMENT of hearing disorders ,GENE therapy ,CONFERENCES & conventions ,REGENERATION (Biology) ,GENES ,GENE expression ,HAIR cells - Abstract
Inner ear hair cell (HC) damage is irreversible in mammals, but is has been shown that supporting cells (SCs) have the potential to differentiate into HCs. Serpine2, a serine protease inhibitor, encodes protease nexin 1, and this has been suggested to be a factor that promotes HC regeneration. In this study, we overexpressed Serpine2 in inner ear SCs cultured in two- and three-dimensional(2D and 3D) systems using the Adeno-associated virus-inner ear (AAV-ie) vector, which promoted organoid expansion and HC differentiation. Overexpression of Serpine2 in the mouse cochlea through the round window membrane (RWM) injection promoted SC proliferation and HC regeneration, and the regenerated HCs were found to be derived from Lgr5+ SCs. In conclusion, our findings indicate that Serpine2 overexpression promotes HC regeneration and suggest that the utilization of inner ear progenitor cells in combination with AAVs might be a promising therapeutic target for hearing restoration. [ABSTRACT FROM AUTHOR]
- Published
- 2024