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Objective: In this study, we investigated the potential of mouse induced pluripotent stem cells (iPSC) for use as a source of transplants for the restoration of auditory hair cells and spiral ganglion neurons., Methods: We co-cultured the mouse iPSC with the cells of the cochlear organ of Corti or the modiolus in vitro. The cochlear organ of Corti (which contains cochlear hair cells) and the modiolus (which contains auditory spiral ganglion neurons) were obtained from postnatal day 3 (P3) CD-1 ICR mice. After 18 days of coculture with the cells of newborn mouse cochleae. The expressions of hair cell markers (Myosin VIIa, Math1, Calretinin, Espin) and Spiral ganglion neuron markers [Nestin, Neurofilament-M, β-III Tubulin, Vesicular glutamate transporter 1(VGluT1)] were detected by immunocytochemical analysis., Results: Immunocytochemical analysis results indicated that the differentiated iPSC expressed auditory hair cell markers (MyosinVIIa,Math1, Calretinin, Espin ) and spiral ganglion markers (Nestin, Neurofilament-M,β-III Tubulin,VGluT1)., Conclusion: Mouse iPSC in virto cultured could successfully be induced to differentiate into hair cell-like cells and spiral ganglion-like cells with hair cell and spiral ganglion molecular markers.

Loss of hair cells in mammals including human beings causes permanent hearing loss because the cochlea cannot regenerate hair cells spontaneously. Here we show that the newborn mouse cochleae contain sphere-forming cells that have the capacity for proliferation in culture, differentiating to form cells that express hair cell markers. When treated with epidermal growth factor or basic fibroblast growth factor, the number of spheres formed increases. The sphere cells express genes that are indicative of inner ear progenitor cells. After differentiation, some sphere cells grow a hair cell bundle-like structure that expresses hair cell marker myosin VIIA and espin. The sphere-forming cells being capable of differentiating into hair cell-like cells implies the possibility of using these sphere-forming cells for reconstructing the damaged cochlear hair cells.

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To investigate the effect and mechanism of Pou4f3 gene mutation on pyroptosis in cochleae of cisplatin-induced deafness mice. Methods: Mice were intraperitoneally injected with cisplatin to construct an animal model of deafness, and sh-Pou4f3 and mutant vector were injected to alter gene expression. TUNEL staining was used to assess the apoptosis level of cochlear hair cells, ELISA was used to detect the secretion of inflammatory factors, and immunofluorescence and Western Blot were used to detect the expression of pyroptosis related factors. Results: Cisplatin induced pyroptosis through NLRP3/Caspase-3/GSDME pathway and significantly down-regulated Pou4f3 level. Pou4f3 mutations promote cochlear hair cell pyroptosis by activating the NLRP3/Caspase-3/GSDME pathway. Knockdown of Pou4f3 can superimpose cisplatin treatment to induce pyroptosis of cochlear hair cells through NLRP3/Caspase-3/GSDME pathway. Conclusion: Pou4f3 gene mutation promotes pyroptosis of cochleae in cisplatin-induced deafness mice through NLRP3/Caspase-3/GSDME pathway. [ABSTRACT FROM AUTHOR]