Autologous cultivated oral mucosal epithelial cell sheets to treat stem cell-deficient vision loss: A multi-centre clinical trial

Limbal epithelial stem cells located at the corneal periphery are essential for maintaining the integrity of the corneal epithelium. Their depletion, known as a limbal stem cell deficiency (LSCD), can cause severe vision loss. Cultivated oral mucosal epithelial cell sheet transplantation (COMET) offers a promising treatment for LSCD. Here, six eyes of six patients underwent COMET in a prospective, multi-centre, government-controlled clinical trial. Only Good Gene, Cellular and Tissue-based Products Manufacturing Practice-compliant cell sheets were used, with follow-up for two years. The primary endpoint, corneal epithelial reconstruction, was successfully achieved in 100% of eyes at one year and 67% at two years. Visual acuity improved in 50% of eyes at both the one and two year examinations, with corneal opacification diminished in 33% and 50% of eyes, respectively. No clinically significant adverse events occurred throughout the whole follow-up period and the efficacy and safety of COMET was thus confirmed. The cell sheet, “Ocural”, is now approved as a Cellular and Tissue-Based Product, the world’s first regenerative medicine product for COMET.Trial registration numbers: UMIN000018662 (https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000021510) registered on 13 August 2015.