Cultivated autologous limbal epithelial cell (CALEC) transplantation: Development of manufacturing process and clinical evaluation of feasibility and safety

To treat unilateral limbal stem cell (LSC) deficiency, we developed cultivated autologous limbal epithelial cells (CALEC) using an innovative xenobiotic-free, serum-free, antibiotic-free, two-step manufacturing process for LSC isolation and expansion onto human amniotic membrane with rigorous quality control in a good manufacturing practices facility. Limbal biopsies were used to generate CALEC constructs, and final grafts were evaluated by noninvasive scanning microscopy and tested for viability and sterility. Cultivated cells maintained epithelial cell phenotype with colony-forming and proliferative capacities. Analysis of LSC biomarkers showed preservation of stemness. After preclinical development, a phase 1 clinical trial enrolled five patients with unilateral LSC deficiency. Four of these patients received CALEC transplants, establishing preliminary feasibility. Clinical case histories are reported, with no primary safety events. On the basis of these results, a second recruitment phase of the trial was opened to provide longer term safety and efficacy data on more patients.

Automated summary

In this study, a novel xenobiotic-free, serum-free, antibiotic-free, two-step process was developed to treat unilateral limbal stem cell (LSC) deficiency. Cultivated autologous limbal epithelial cells (CALEC) were generated from limbal biopsies and expanded onto human amniotic membrane with rigorous quality control. The clinical trial showed preliminary feasibility and safety of CALEC transplants in patients with unilateral LSC deficiency, leading to a second phase of recruitment to collect longer term safety and efficacy data.