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Clinical trial of autologous cultivated limbal epithelial cell sheet transplantation for patients with limbal stem cell deficiency

Oie, Yoshinori, Sugita, Seiichiro, Yokokura, Shunji, Nakazawa, Toru, Tomida, Daisuke, Satake, Yoshiyuki, Shimazaki, Jun, Hara, Yuko, Shiraishi, Atsushi, Quantock, Andrew J. ORCID:, Ogasawara, Takahiro, Inoie, Masukazu and Nishida, Kohji 2023. Clinical trial of autologous cultivated limbal epithelial cell sheet transplantation for patients with limbal stem cell deficiency. Ophthalmology 130 (6) , pp. 608-614. 10.1016/j.ophtha.2023.01.016
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Objective or Purpose To confirm the efficacy and safety of Good Manufacturing Practice (GMP)-compliant autologous cultivated limbal epithelial cell sheets in government-controlled clinical trials that adhered to Good Clinical Practice stipulations for patients with unilateral limbal stem cell deficiency (LSCD). Design A prospective, multi-center, open-label, uncontrolled, single-arm clinical trial. Subjects, Participants or Controls Ten consecutive eyes of 10 patients with unilateral LSCD were followed for two years after surgery. Preoperative LSCD stage was IIB in four eyes and III in six eyes. Methods A limbal tissue biopsy was obtained from the healthy eye, after which limbal stem cells were dissociated and cultivated on temperature-responsive culture surfaces. All cell sheets were fabricated in a GMP-grade facility under established standard operating procedures. Cell sheets were evaluated using defined shipment criteria before transplantation, and only those that met the criteria were used. The cell sheet was transplanted onto each of the patients' diseased eye after removing the conjunctival scar tissue that covered the corneal surface. The severity of LSCD was determined according to a staging method agreed upon by global consensus, with eyes evaluated as being in stages IA–C representing successful corneal epithelial reconstruction. LSCD diagnosis and staging were determined by the trial's Eligibility Judgment Committee and Effect Assessment Committee using slit-lamp photographs including fluorescein staining. Both committees comprised two or three third-party cornea specialists, who were provided with information anonymously and randomly. Main Outcome Measure Corneal epithelial reconstruction rate was the primary endpoint. Results Corneal epithelial reconstruction was successful in six of 10 eyes (60%) one year postoperatively and was significantly higher than the 15% clinically significant efficacy rate achieved by allogeneic limbal transplantation. The reconstruction rate was 70% of eyes two years postoperatively. Additionally, improvements in visual acuity were noted in 50% and 60% of eyes at one and two years, respectively. No clinically significant transplantation-related adverse events were observed. Conclusion The efficacy and safety of cultivated limbal epithelial cell sheet transplantation were thus confirmed, and the cell sheet, named Nepic, is now approved as a Cellular and Tissue-Based Product in Japan.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Optometry and Vision Sciences
Additional Information: License information from Publisher: LICENSE 1: Title: This article is under embargo with an end date yet to be finalised.
Publisher: Elsevier
ISSN: 0161-6420
Date of First Compliant Deposit: 2 March 2023
Date of Acceptance: 13 January 2023
Last Modified: 31 May 2023 13:42

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