Abstract

Recent advancements in stem cell therapy have led to an increased interest within the auditory community in exploring the potential of mesenchymal stem cells (MSCs) in the treatment of inner ear disorders. However, the biocompatibility of MSCs with the inner ear, especially when delivered non-surgically and in the immunocompetent cochlea, is not completely understood. In this study, we determined the effect of intratympanic administration of rodent bone marrow MSCs (BM-MSCs) on the inner ear in an immunocompetent rat model. The administration of MSCs did not lead to the generation of any oxidative stress in the rat inner ear. There was no significant production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-12, due to BM-MSCs administration into the rat cochlea. BM-MSCs do not activate caspase 3 pathway, which plays a central role in sensory cell damage. Additionally, transferase dUTP nick end labeling (TUNEL) staining determined that there was no significant cell death associated with the administration of BM-MSCs. The results of the present study suggest that trans-tympanic administration of BM-MSCs does not result in oxidative stress or inflammatory response in the immunocompetent rat cochlea.

Highlights

  • Auditory disorders and hearing loss affect a significant proportion of the human population [1,2,3]

  • Tr8a‐nissotypmropsatnainceAidsmaiwniesltlr‐aatciocnepotfeBdMm-MarkSeCrsfdoor nooxtidInadtiuvcee sOtrxeisdsatiinvethSetrceosschinleRaa[t3C7,o3c8h]l.eTa herefore, the levels of 8‐isoprostane in whole cochlear tissue homogenates were determined by ELISA at 3, 5, 7, 14 and 83-0isdoapyropsotasnt‐eadismainwisetlrla-taicocnep(Fteigdumrea1r)k.eTrhfeorreowxiadsantiovestsattrisetsiscainllythseigcnoifcihcalenat [d3i7ff,3e8re].ncTehienrelefovreels, 1toph4feear8lni‐eoidvsdeo3slp0s(rpdoofa>syt80a-.pni0soe5os)pbt.-eraotwdstmeaeninneiBsintMraw‐tMihoonSlCe(Fsciotgrcueharleetea1dr),.tPiTsBshuSeerienhjwoecmatseodng,oecnsoatnatettrissotwlicaeanrledlydcseoitgnentrrmiafilicanatenedrtadbliygffrEeorLueInpScsAeaaitnta3llel, vt5ie,ml7se, of 8-isoprostane between BM-mesenchymal stem cells (MSCs) treated, phosphate buffered saline (PBS) injected, control and contralateral groups at all time periods (p > 0.05)

  • There was no statistically significant difference in mean signal intensity of cleaved caspase 3 staining between BM‐MSCs treated, PBS injected and 3c.o3.nBtrMol-gMroSuCpssdi(dp n>o0t.T0r5i)g(gFeirgPurroein2flBa)m. matory Cytokine Production in rat Cochlea

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Summary

Introduction

Auditory disorders and hearing loss affect a significant proportion of the human population [1,2,3]. Of American adults over age 18, 15% report having some difficulty in hearing [4]. Factors such as age, noise trauma, infection, and ototoxic drugs can lead to damage of sensory auditory hair cells in the inner ear (cochlea), leading to hearing impairment [4,5,6]. Any perturbation of the sound pathway can lead to hearing impairment. Sensorineural hearing loss (SNHL) predominantly results from damage to the auditory hair cells. The prevalence of SNHL increases with age and it is the most common type of hearing loss in adults over 65 years old, occurring in 23% of adults in that age range [7,8]. Hearing aids are unpopular due to poor fitting, cosmetic issues, and fear of social stigmatization [12,13]

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