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Sutureless Transplantation of Autologous Oral Mucosa Epithelial Cells in Corneal Reconstruction

Sutureless Transplantation of Autologous Oral Mucosa Epithelial Cells in Corneal Reconstruction Abstract New England Journal of Medicine Corneal Reconstruction With Tissue-Engineered Cell Sheets Composed of Autologous Oral Mucosal Epithelium: A New Approach to Ocular Surface Reconstruction in Bilateral Limbal Stem Cell Deficiency Kohji Nishida, MD, PhD; Masayuki Yamato, PhD; Yasutaka Hayashida, MD; Katsuhiko Watanabe, MSc; Kazuaki Yamamoto, MSc; Eijiro Adachi, MD, PhD; Shigeru Nagai, MSc; Akihiko Kikuchi, PhD; Naoyuki Maeda, MD, PhD; Hitoshi Watanabe, MD, PhD; Teruo Okano, PhD; Yasuo Tano, MD, PhD 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. N Engl J Med. 2004;351:1187-1196. When ophthalmology articles are published in the New England Journal of Medicine they usually are important. At first it was surprising that a small case series of 4 patients with grafts of mucosal cells for bilateral limbal stem cell deficiency was published in this journal. But the article does report impressive results using autologous oral mucosa as a source of epithelial cells for special tissue culture treatment prior to sutureless and carrier-free transplantation onto the cornea. This approach may represent a huge advance in the visual rehabilitation of people with several bilateral limbal stem cell deficiency. The oral mucosa is a readily available source of cells, except for patients with oral mucosal involvement in their disease. The tissue culture techniques used are not readily available, but mucosal specimens could perhaps be transported for special processing. Limbal allografts are currently performed for bilateral limbal stem cell deficiency, but they have the disadvantage of requiring lifelong systemic immunosuppression and are least successful in patients with Stevens-Johnson syndrome and ocular cicatricial pemphigoid.1,2 This article reports dramatic success in 4 patients with these devastating diagnoses, 3 of whom had failed previous procedures and severe aqueous deficiency dry eyes. Although the postoperative assessments were made by investigators who did not know whether the procedure had been performed, I think it would be hard for the observers not to know. Histologic examination confirms that the cultured cells look like corneal epithelial cells, and the basal cells stain positively for epithelial stem cell markers. The authors do not explain how their method works to isolate and grow epithelial stem cells for the conjunctiva from oral mucosal specimens. The actual transplantation procedure appears straightforward. The outcomes after a minimum of 1 year follow-up are very encouraging with regard to both corneal clarity and improvement in vision. Hopefully, additional studies will confirm and extend these promising results. Correspondence: Dr Cohen, Cornea Service, Wills Eye Hospital, 840 Walnut St, Suite 920, Philadelphia, PA 19107 (ecohen@willsee.org). References 1. Schwartz GSTsubota KTseng SCGMannis MJHolland EJ Keratolimbal allograft. Holland EJMannis MJ Ocular Surface Disease New York, NY Springer-Verlag2002;208- 222Google Scholar 2. Samson CMNduaguba CBaltatzis SFoster CS Limbal stem cell transplantation in chronic inflammatory eye disease. Ophthalmology 2002;109862- 868PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Sutureless Transplantation of Autologous Oral Mucosa Epithelial Cells in Corneal Reconstruction

Archives of Ophthalmology , Volume 123 (7) – Jul 1, 2005

Sutureless Transplantation of Autologous Oral Mucosa Epithelial Cells in Corneal Reconstruction

Abstract

Abstract New England Journal of Medicine Corneal Reconstruction With Tissue-Engineered Cell Sheets Composed of Autologous Oral Mucosal Epithelium: A New Approach to Ocular Surface Reconstruction in Bilateral Limbal Stem Cell Deficiency Kohji Nishida, MD, PhD; Masayuki Yamato, PhD; Yasutaka Hayashida, MD; Katsuhiko Watanabe, MSc; Kazuaki Yamamoto, MSc; Eijiro Adachi, MD, PhD; Shigeru Nagai, MSc; Akihiko Kikuchi, PhD; Naoyuki Maeda, MD, PhD; Hitoshi Watanabe, MD, PhD; Teruo Okano, PhD; Yasuo...
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Publisher
American Medical Association
Copyright
Copyright © 2005 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.123.7.1002
Publisher site
See Article on Publisher Site

Abstract

Abstract New England Journal of Medicine Corneal Reconstruction With Tissue-Engineered Cell Sheets Composed of Autologous Oral Mucosal Epithelium: A New Approach to Ocular Surface Reconstruction in Bilateral Limbal Stem Cell Deficiency Kohji Nishida, MD, PhD; Masayuki Yamato, PhD; Yasutaka Hayashida, MD; Katsuhiko Watanabe, MSc; Kazuaki Yamamoto, MSc; Eijiro Adachi, MD, PhD; Shigeru Nagai, MSc; Akihiko Kikuchi, PhD; Naoyuki Maeda, MD, PhD; Hitoshi Watanabe, MD, PhD; Teruo Okano, PhD; Yasuo Tano, MD, PhD 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. N Engl J Med. 2004;351:1187-1196. When ophthalmology articles are published in the New England Journal of Medicine they usually are important. At first it was surprising that a small case series of 4 patients with grafts of mucosal cells for bilateral limbal stem cell deficiency was published in this journal. But the article does report impressive results using autologous oral mucosa as a source of epithelial cells for special tissue culture treatment prior to sutureless and carrier-free transplantation onto the cornea. This approach may represent a huge advance in the visual rehabilitation of people with several bilateral limbal stem cell deficiency. The oral mucosa is a readily available source of cells, except for patients with oral mucosal involvement in their disease. The tissue culture techniques used are not readily available, but mucosal specimens could perhaps be transported for special processing. Limbal allografts are currently performed for bilateral limbal stem cell deficiency, but they have the disadvantage of requiring lifelong systemic immunosuppression and are least successful in patients with Stevens-Johnson syndrome and ocular cicatricial pemphigoid.1,2 This article reports dramatic success in 4 patients with these devastating diagnoses, 3 of whom had failed previous procedures and severe aqueous deficiency dry eyes. Although the postoperative assessments were made by investigators who did not know whether the procedure had been performed, I think it would be hard for the observers not to know. Histologic examination confirms that the cultured cells look like corneal epithelial cells, and the basal cells stain positively for epithelial stem cell markers. The authors do not explain how their method works to isolate and grow epithelial stem cells for the conjunctiva from oral mucosal specimens. The actual transplantation procedure appears straightforward. The outcomes after a minimum of 1 year follow-up are very encouraging with regard to both corneal clarity and improvement in vision. Hopefully, additional studies will confirm and extend these promising results. Correspondence: Dr Cohen, Cornea Service, Wills Eye Hospital, 840 Walnut St, Suite 920, Philadelphia, PA 19107 (ecohen@willsee.org). References 1. Schwartz GSTsubota KTseng SCGMannis MJHolland EJ Keratolimbal allograft. Holland EJMannis MJ Ocular Surface Disease New York, NY Springer-Verlag2002;208- 222Google Scholar 2. Samson CMNduaguba CBaltatzis SFoster CS Limbal stem cell transplantation in chronic inflammatory eye disease. Ophthalmology 2002;109862- 868PubMedGoogle ScholarCrossref

Journal

Archives of OphthalmologyAmerican Medical Association

Published: Jul 1, 2005

Keywords: oral mucous membrane,reconstructive surgical procedures,cornea,transplantation,epithelial cells,allografting,therapeutic immunosuppression,follow-up,postoperative care,surgical procedures, operative,sutures,cell culture techniques,blindness,corneal opacity,kikuchi's disease,ocular trauma,mitomycin,body temperature,eye,epithelial stem cells,conjunctiva,new england

References