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.