June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Clinical Trial of Autologous Cultivated Oral Mucosal Epithelial Cell Sheet Transplantation for Limbal Stem Cell Deficiency
Author Affiliations & Notes
  • Yoshinori Oie
    Ophthalmology, Osaka Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Suita, Osaka, Japan
  • Shunji Yokokura
    Ophthalmology, Tohoku Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Sendai, Miyagi, Japan
  • Toru Nakazawa
    Ophthalmology, Tohoku Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Sendai, Miyagi, Japan
  • Tomohiko Usui
    Tokyo Daigaku Daigakuin Igakukei Kenkyuka Igakubu Seirigaku, Bunkyo-ku, Tokyo, Japan
  • Shiro Amano
    Tokyo Daigaku Daigakuin Igakukei Kenkyuka Igakubu Seirigaku, Bunkyo-ku, Tokyo, Japan
  • Hiroshi Takayanagi
    Ophthalmology, Osaka Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Suita, Osaka, Japan
  • Shoko Matsubara
    Ophthalmology, Osaka Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Suita, Osaka, Japan
  • Kiyoshi Okada
    Osaka Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Suita, Osaka, Japan
  • Takeshi Soma
    Ophthalmology, Osaka Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Suita, Osaka, Japan
  • Takahiro Ogasawara
    Kabushiki Kaisha Japan Tissue Engineering, Gamagori, Aichi, Japan
  • Masukazu Inoie
    Kabushiki Kaisha Japan Tissue Engineering, Gamagori, Aichi, Japan
  • Andrew Quantock
    Cardiff University, Cardiff, Cardiff, United Kingdom
  • Kohji Nishida
    Ophthalmology, Osaka Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Suita, Osaka, Japan
  • Footnotes
    Commercial Relationships   Yoshinori Oie Santen, Code R (Recipient), Senju, Code R (Recipient), Novartis, Code R (Recipient), Japan Tissue Engineering, Code R (Recipient), Nidek, Code R (Recipient), GlaxoSmithKline, Code R (Recipient); Shunji Yokokura None; Toru Nakazawa None; Tomohiko Usui None; Shiro Amano None; Hiroshi Takayanagi None; Shoko Matsubara None; Kiyoshi Okada None; Takeshi Soma None; Takahiro Ogasawara Japan Tissue Engineering, Code E (Employment); Masukazu Inoie Japan Tissue Engineering, Code E (Employment); Andrew Quantock None; Kohji Nishida Japan Tissue Engineering, Code C (Consultant/Contractor)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2347. doi:
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      Yoshinori Oie, Shunji Yokokura, Toru Nakazawa, Tomohiko Usui, Shiro Amano, Hiroshi Takayanagi, Shoko Matsubara, Kiyoshi Okada, Takeshi Soma, Takahiro Ogasawara, Masukazu Inoie, Andrew Quantock, Kohji Nishida; Clinical Trial of Autologous Cultivated Oral Mucosal Epithelial Cell Sheet Transplantation for Limbal Stem Cell Deficiency. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2347.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The corneal epithelium at the limbus at the edge of the cornea contains basally located stem cells that replenish and maintain the epithelium throughout life. Injury or disease, however, can lead to a limbal stem cell deficiency (LSCD) whereby vision is severely impaired because of corneal epithelial malformation, corneal opacification and neovascularization. Transplantation of ex-vivo expanded autologous oral mucosal epithelial cell sheets represents a promising approach to restore the sight of patients with LSCD.

Methods : A prospective, multi-center, government-controlled clinical trial was conducted using GCTP-compliant autologous cultivated oral mucosal epithelial cell sheets to investigate efficacy and safety. Six consecutive eyes of six bilateral Stage III LSCD patients underwent surgery and were followed for two years. All cell sheets were fabricated in a GCTP-grade facility under established standard operating procedures, guided and recorded under a process management system. Cell sheets were evaluated using defined shipment criteria before transplantation, and only cell sheets that met the criteria were used for transplantation. As the primary endpoint, corneal epithelial reconstruction was evaluated by a third-party committee composed of three cornea specialists.

Results : The mean age of the patients was 59±27 years at the time of enrollment, with three males and three females included. LSCD was caused by mucous membrane pemphigoid (n=2) and Steven-Johnson syndrome (n=2) in four of the six patients, with one suffering from aniridia and the other idiopathic. The corneal epithelium was successfully reconstructed in 100% of the eyes one year post-operatively and in 67% of the eyes two years post-operatively. Respectively, at years one and two, visual acuity had improved in 50% and 50% of eyes, corneal opacification had improved in 33% and 50% of eyes, with neovascularization improving in 50% and 50% of eyes. No clinically significant adverse events related to the transplantation were experienced.

Conclusions : In this trial, conducted under strict regulatory control, the efficacy and safety of cultivated oral mucosal epithelial cell sheet transplantation was confirmed. The cell sheet, called Ocural, is now approved as a Cellular and Tissue-Based Product, world’s first regenerative medicine product of a cultivated oral mucosal cell sheet for use in ophthalmology.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

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