Abstract

Tympanic membrane (TM) perforation, in particular chronic otitis media, is one of the most common clinical problems in the world and can present with sensorineural healing loss. Here, we explored an approach for TM regeneration where the latent progenitor or stem cells within TM epithelial layers may play an important regulatory role. We showed that potential TM stem cells present highly positive staining for epithelial stem cell markers in all areas of normal TM tissue. Additionally, they are present at high levels in perforated TMs, especially in proximity to the holes, regardless of acute or chronic status, suggesting that TM stem cells may be a potential factor for TM regeneration. Our study suggests that latent TM stem cells could be potential regulators of regeneration, which provides a new insight into this clinically important process and a potential target for new therapies for chronic otitis media and other eardrum injuries.

Highlights

  • Studies showed some potentials for acute TM regeneration, it should be noted that no definite treatment alternatives to surgery for chronic TM perforations have been reported until now

  • Further studies of TM stem cell markers are required to identify the exact stem cells in the TM, we demonstrated that potential stem cells in the TM present high expression of epithelial stem cell markers and proliferation markers

  • The epidermal stem cell markers integrin β 1 (INGβ 1) and cytokeratin 19 (CK19) were highly expressed during the period of perforation; their expression decreased to normal levels after the perforations healed

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Summary

Introduction

Studies showed some potentials for acute TM regeneration, it should be noted that no definite treatment alternatives to surgery for chronic TM perforations have been reported until now. To address this challenge, here, we propose a novel approach for regeneration of the TM in both acute and chronic TM perforations without surgical treatments. This study was composed of two parts: 1) identification of TM stem cells using epithelial stem cell markers; 2) investigation of the distribution of TM stem cells in the normal TM and in the TM during regeneration in both acute and chronic perforations. We found that TM stem cells regulated TM regeneration in both acute and chronic perforations, demonstrating a potential therapy for TM rupture and full hearing restoration

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