Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium

N Engl J Med. 2004 Sep 16;351(12):1187-96. doi: 10.1056/NEJMoa040455.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cells, Cultured
  • Corneal Diseases / surgery*
  • Epithelial Cells / transplantation*
  • Epithelium, Corneal / pathology
  • Epithelium, Corneal / surgery
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mouth Mucosa / cytology*
  • Mouth Mucosa / transplantation
  • Pemphigoid, Benign Mucous Membrane / surgery*
  • Stem Cell Transplantation*
  • Stevens-Johnson Syndrome / surgery*
  • Tissue Engineering / methods*
  • Transplantation, Autologous