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Middle ear mucosal regeneration by tissue-engineered cell sheet transplantation

Kazuhisa Yamamoto,M. Yamato,Tsunetaro Morino,H. Sugiyama,R. Takagi,Y. Yaguchi,T. Okano,H. Kojima

Published 2017 in npj Regenerative Medicine

ABSTRACT

The recurrence of cholesteatoma after surgical treatment often occurs as a result of poor mucosal regeneration in the middle ear cavity and mastoid cavity and changes, such as granulation tissue formation, which impair gas exchange in the middle ear cavity. Conventional 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 the middle ear mucosa can be preserved or rapid postoperative regeneration of mucosa on the exposed bone surface can be achieved after middle ear surgery, the results of surgical treatment for otitis media, including cholesteatoma, can potentially be improved and the physiological function of the middle ear can be recovered. 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. In clinical research, we endoscopically removed an approximately 10 × 10 mm2 piece of nasal mucosal tissue. 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 attic of the tympanic and mastoid cavities 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 and the patients’ hearing ability post-transplantation remained good. Transplanting a sheet of cells from the nose to the middle ear could improve postoperative prognosis for middle ear inflammatory conditions. Kazuhisa Yamamoto of Jikei University School of Medicine and colleagues in Japan developed a novel surgical technique to prevent postoperative recurrence of chronic middle ear conditions. In adhesive otitis media, the eardrum gets sucked into and stuck in the middle ear space. Cholesteatoma involves abnormal skin growth in the middle ear. Recurrence often follows surgical treatment for these conditions due to delays in regeneration of the middle ear’s mucosal epithelium. The new technique involves transplanting cultured cells from the lining of the nasal cavity to the middle ear during surgery. Five patients treated this way had favorable postoperative outcomes with no adverse effects or complications and satisfactory improvement in hearing levels.

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