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Original Article
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Volume 351:1187-1196 September 16, 2004 Number 12
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Corneal Reconstruction with Tissue-Engineered Cell Sheets Composed of Autologous Oral Mucosal Epithelium
Kohji Nishida, M.D., Ph.D., Masayuki Yamato, Ph.D., Yasutaka Hayashida, M.D., Katsuhiko Watanabe, M.Sc., Kazuaki Yamamoto, M.Sc., Eijiro Adachi, M.D., Ph.D., Shigeru Nagai, M.Sc., Akihiko Kikuchi, Ph.D., Naoyuki Maeda, M.D., Ph.D., Hitoshi Watanabe, M.D., Ph.D., Teruo Okano, Ph.D., and Yasuo Tano, M.D., Ph.D.

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 by Pellegrini, G.

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ABSTRACT

Background Ocular trauma or disease may lead to severe corneal opacification and, consequently, severe loss of vision as a result of complete loss of corneal epithelial stem cells. Transplantation of autologous corneal stem-cell sources is an alternative to allograft transplantation and does not require immunosuppression, but it is not possible in many cases in which bilateral disease produces total corneal stem-cell deficiency in both eyes. We studied the use of autologous oral mucosal epithelial cells as a source of cells for the reconstruction of the corneal surface.

Methods We harvested 3-by-3-mm specimens of oral mucosal tissue from four patients with bilateral total corneal stem-cell deficiencies. Tissue-engineered epithelial-cell sheets were fabricated ex vivo by culturing harvested cells for two weeks on temperature-responsive cell-culture surfaces with 3T3 feeder cells that had been treated with mitomycin C. After conjunctival fibrovascular tissue had been surgically removed from the ocular surface, sheets of cultured autologous cells that had been harvested with a simple reduced-temperature treatment were transplanted directly to the denuded corneal surfaces (one eye of each patient) without sutures.

Results Complete reepithelialization of the corneal surfaces occurred within one week in all four treated eyes. Corneal transparency was restored and postoperative visual acuity improved remarkably in all four eyes. During a mean follow-up period of 14 months, all corneal surfaces remained transparent. There were no complications.

Conclusions Sutureless transplantation of carrier-free cell sheets composed of autologous oral mucosal epithelial cells may be used to reconstruct corneal surfaces and can restore vision in patients with bilateral severe disorders of the ocular surface.


Source Information

From the Department of Ophthalmology, Osaka University Medical School, Osaka (K.N., Y.H., K.W., K.Y., N.M., H.W., Y.T.); the Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo (M.Y., S.N., A.K., T.O.); and the Department of Molecular Morphology, Kitasato University Graduate School of Medicine, Kanagawa (E.A.) — all in Japan.

Address reprint requests to Dr. Nishida at the Department of Ophthalmology, Osaka University Medical School, Room E7, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan, or at knishida{at}ophthal.med.osaka-u.ac.jp.

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