Long-term outcomes of middle ear regenerative therapy using cell sheet transplantation combined with tympanoplasty.

INTRODUCTION

Regenerative medicine using autologous mucosa-derived epithelial cell sheets has attracted increasing attention as a novel therapeutic strategy for reconstructing epithelial tissues. We have developed a new regenerative treatment for middle ear diseases, including cholesteatoma, using autologous nasal mucosal epithelial cell sheets, and conducted clinical studies demonstrating its potential to suppress postoperative recurrence. In this study, we evaluated the long-term clinical outcomes of patients treated with this approach.

METHODS

In our clinical research project, six patients with acquired cholesteatoma underwent canal wall up tympanoplasty with mastoidectomy combined with autologous nasal mucosal epithelial cell sheet transplantation between 2014 and 2019. Four patients who were followed up for more than five years after transplantation were included in this long-term analysis. Postoperative outcomes were assessed based on mastoid cavity aeration on computed tomography (CT), hearing outcomes, recurrence of cholesteatoma, and transplantation-related adverse events.

RESULTS

Mean follow-up was 9.25 years (range: 6.5-11.5 years). All patients maintained successful mastoid aeration throughout the study, with mean CT areas of 216.08 ± 75.87 mm2 at 2 years and 193.80 ± 71.41 mm2 beyond 5 years postoperatively. No cholesteatoma recurrence or tympanic membrane retraction was observed. Hearing levels improved and remained stable during long-term follow-up. No serious complications, allergic reactions, or signs of malignant transformation were identified.

CONCLUSION

Canal wall up tympanoplasty with mastoidectomy combined with autologous nasal mucosal epithelial cell sheet transplantation is a safe and effective long-term regenerative treatment for middle ear diseases. This therapy contributes to sustained aeration and prevention of recurrence through regeneration of the middle ear mucosa and may represent the first regenerative medicine product for clinical application in otology.