Cultivated Autologous Limbal Epithelial Cell Transplantation: A Comprehensive Review of Clinical Trials and Applications.

Purpose: Limbal stem cells (LSCs) are essential for corneal epithelial regeneration and ocular surface homeostasis. Dysfunction of LSCs results in LSC deficiency (LSCD), a leading cause of global blindness. Although ex vivo expansion and autologous transplantation of LSCs have demonstrated promising clinical outcomes, no Food and Drug Administration-approved therapies for LSCD are available in the United States. To address this gap, we developed a novel 2-step process for isolating and expanding LSCs on human amniotic membrane under good manufacturing practice conditions, using a xenobiotic-free, serum-free, and antibiotic-free environment.

Methods: Autologous limbal biopsies were used to generate cultivated autologous limbal epithelial cell (CALEC) constructs, ensuring rigorous safety and efficacy measures. Furthermore, we compared the success rates of good manufacturing practice-manufactured cultivated limbal epithelial transplantation (CLET) products with those of CALEC.

Results: Among 16 limbal biopsies harvested from 15 participants, 14 resulted in successful manufacturing of CALEC grafts. Phase I clinical trial demonstrated preliminary feasibility and no safety concerns. In the phase II trial, 92% of grafts showed partial or complete success at 18 months, with no safety issues. The success rate of CALEC grafts was comparable to currently available CLET products.

Conclusions: The findings underscore the safety and efficacy of CALEC transplantation as a promising therapeutic strategy for LSCD. The current review focuses on the manufacturing, quality control, and clinical performance of CALEC constructs in phase I/II trials for unilateral LSCD, paving the way for future trials in advancing LSC-based regenerative therapies in the United States.