Abstract:

Aims: Ototoxicity is one of the main side effects of the chemotherapeutic agent Cisplatin CDDP . CDDP ototoxicity is caused by damage of the organ of Corti, spiral ganglion cells or lateral wall stria vascularis and spiral ligament . Mesenchymal stem cells MSCs were shown to differentiate into neurogenic and auditory hair cells in vitro. In this study, effect of MSCs in CDDP ototoxicity model of HEI-OC1 cochlear cells was evaluated. Method: The cochlear cells were exposed to 50 and 100 microM CDDP for 24, 48, 72 hours with and without MSCs as coculture. The viability of the cells was analyzed with trypan blue dye and the percentage of apoptosis with Annexin-V by flow cytometer. The differentiation of MSCs to immature cochlear cells were shown by Math1, Calretinin and Myosin IIa immunohistochemistry. Results: At 100 microM dose, CDDP caused cytotoxicity on cochlear cells predominantly via necrosis. In co-culture, MSCs decreased cochlear cell damage of CDDP. In co-culture the ratio of Math1 and calretinin positive cells were increased supporting the idea of differentiation of MSCs into immature hair cells. Conclusion: In this in vitro study, our data support that MSCs protects cochlear cells from CDDP cytotoxicity. MSC therapy might be a candidate cellular therapy approach to overcome CDDP ototoxicity. The mechanism seems to be via differentiation of MSCs into immature hair cells. Our next step is to plan in vivo nude mice neuroblastoma animal model comparing CDDP therapy with and without systemic MSC administration and check ototoxicity.

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