Realization of middle ear mucosal regeneration by cultured nasal mucosal epithelial cell sheet transplantation

Abstract

Recurrence of cholesteatoma is mainly caused by poor mucosal regeneration in the middle ear cavity and mastoid cavity. Conventional canal wall up tympanoplasty often results in a lack of mucosal regeneration in the resected area of the mastoid cavity. In particular, mucosal regeneration in a poorly pneumatized mastoid cavity is extremely difficult. If regeneration of the damaged middle ear mucosa were possible in the early postoperative period, it would be possible to prevent re-adhesion of the tympanic membrane and recurrence of adhesive otitis media. Additionally, regeneration of middle ear mucosa would prevent recurrence of cholesteatoma. To overcome these limitations, we developed a novel treatment method combining tympanoplasty and autologous nasal mucosal epithelial cell sheet transplantation for postoperative regeneration of the middle ear mucosa. Tissue-engineered autologous nasal mucosal epithelial cell sheets were fabricated by culturing the harvested cells in an aseptic environment in a good manufacturing practice-compliant cell processing facility. The cultivated cell sheets were transplanted, during tympanoplasty, onto the exposed bony surface of the middle ear cavity where the mucosa had been lost. We performed this procedure on four patients with middle ear cholesteatoma and one patient with adhesive otitis media. All patients showed favorable postoperative course with no adverse events or complications. To our knowledge, this clinical research is the world’s first-in-human study to transplant cultured cells into the human middle ear. This treatment simultaneously preserves the external ear canal morphology, as in standard canal wall up tympanoplasty, and incorporates autologous cell sheet transplantation, which enables prevention of recurrence of cholesteatoma. This study represents a great step forward in the development of a new surgical approach for treating adhesive otitis media and cholesteatoma.