Cultivated Autologous Limbal Epithelial Cell (CALEC) Transplantation: Development of Manufacturing Process and Clinical Evaluation of Feasibility and Safety

Authors

Ula V Jurkunas
Jia Yin
Lynette K Johns
Sanming Li
Helene Negre
Kit L Shaw
Lassana Samarakoon
Allison R Ayala
Ahmad Kheirkhah
Kishore Katikireddy
Alex Gauthier
Stephan Ong Tone
Aaron R Kaufman
Stacey Ellender
Diego E Hernandez Rodriguez
Heather Daley
Reza Dana
Myriam Armant
Jerome Ritz

Publication Date

8-18-2023

Journal

Science Advances

Abstract

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.

Keywords

Humans, Feasibility Studies, Anti-Bacterial Agents, Biopsy, Commerce, Epithelial Cells, Limbal Stem Cell Deficiency

Comments

PMID: 37595035