Scientists have developed a new treatment to restore vision in people with severe corneal damage caused by the loss of stem cells essential for eye regeneration (LSCD). The procedure, called CALEC, uses the patient’s own cells grown in a laboratory and has been shown to be safe and effective in a clinical trial. Most patients experienced significant improvements in vision and symptoms. The research paves the way for new treatment options and could benefit many people in the future.
The cornea, the clear part of the eye that allows light to pass through, needs to be kept healthy at all times to ensure clear vision. This depends on a special group of cells called limbal epithelial stem cells, which live in the corneal limbus (the transition area between the cornea and the conjunctiva, the white part of the eye).
These cells help to regenerate the outer layer of the cornea and keep it protected. When these cells are damaged or destroyed, Limbal Stem Cell Deficiency (LSCD) occurs, a serious condition that can lead to blindness.
Symptoms include inflammation, abnormal blood vessel growth in the cornea, scarring, blurred vision, and severe eye discomfort, such as pain and sensitivity to light.
Treatment for Limbal Stem Cell Deficiency aims to restore the healthy surface of the eye and restore the function of these stem cells. When only one eye is affected, doctors may remove a small piece of healthy tissue from the patient's own good eye for transplant, avoiding the need for donors and reducing the need for immunosuppressive medications.
There are different forms of transplantation, including direct tissue grafting: conjunctival limbal autograft (CLAU) and simple limbal epithelial transplantation (SLET) and laboratory-grown cell transplantation (CLET).
The laboratory-grown cell transplantation method allows stem cells to be expanded in the laboratory before transplantation, reducing the risk of compromising the healthy eye. However, this procedure is not yet approved in the United States due to the lack of specific regulations and clinical studies.
To overcome this barrier, scientists have developed a new technique called cultured autologous limbal epithelial cell transplantation (CALEC).
This image shows, in a simplified way, how the CALEC transplant process works to treat blindness caused by corneal stem cell deficiency.
First, doctors remove a small sample of tissue from the patient's healthy eye. Then, the cells from this sample are isolated and grown in the laboratory on a special membrane.
This growth occurs in two stages until the cells are ready to be transplanted into the diseased eye, helping to regenerate the ocular surface. Graphs are also shown that analyze the relationship between cell growth and cellular energy, in addition to the time required for the process.
This innovative method follows strict standards required by the FDA (US regulatory agency) and does not use components of animal origin or third-party cells. Researchers conducted a clinical study to evaluate the safety and feasibility of this transplant in patients with Limbal Stem Cell Deficiency in only one eye.
The study involved 15 participants, aged between 24 and 78 years, who were followed for up to 18 months after the transplant. The main objectives were to check whether the transplanted cells survived and whether there were serious side effects, such as infections or graft rejection.
Principal investigator Ula Jurkunas, MD, performs the first stem cell transplant in the CALEC clinical trial in 2018 at Mass Eye and Ear in Boston, on a patient who suffered a severe chemical burn to the eye. Credit: Mass Eye and Ear
The results were promising: 93% of grafts were successful, and most patients experienced improvement in corneal surface and visual symptoms.
Only one patient had an eye infection unrelated to treatment. Overall, 86% of participants showed significant improvement in the first three months, and that rate increased to more than 90% after one year.
The results indicate that cultured autologous limbal epithelial cell (CALEC) transplantation is safe and has great potential for restoring vision in patients with Limbal Stem Cell Deficiency. However, more studies are needed to confirm its long-term efficacy and enable its approval as a treatment available to more people in the future.
READ MORE:
Cultivated autologous limbal epithelial cell (CALEC) transplantation for limbal tem cell deficiency: a phase I/II clinical trial of the first xenobiotic-free, serum-free, antibiotic-free manufacturing protocol developed in the US
Ula V. Jurkunas, Aaron R. Kaufman, Jia Yin, Allison Ayala, Maureen Maguire, Lassana Samarakoon, Lynette K. Johns, Mohit Parekh, Sanming Li, Alex Gauthier, Helene Negre, Kit L. Shaw, Diego E. Hernandez Rodriguez, Heather Daley, Reza Dana, Myriam Armant and Jerome Ritz
Nature Communications. 4 March 2025, 1607 (2025)
DOI: 10.1038/s41467-025-56461-1
Abstract:
We developed a two-stage manufacturing process utilizing cultivated autologous limbal epithelial cells (CALEC), the first xenobiotic-free, serum-free, antibiotic-free protocol developed in the United States, to treat blindness caused by unilateral limbal stem cell deficiency (LSCD) and conducted a single-center, single-arm, phase I/II clinical trial. Primary outcomes were feasibility (meeting release criteria) and safety (ocular infection, corneal perforation, or graft detachment). Participant eligibility included male or female participants age 18 to <90 years old and ability to provide written informed consent with LSCD. Funding was provided by the National Eye Institute of the National Institutes of Health. CALEC grafts met release criteria in 14 (93%) of 15 participants at conclusion of trial. After first stage manufacturing, intracellular adenosine triphosphate levels correlated with colony forming efficiency (r = 0.65, 95% CI [0.04, 0.89]). One bacterial infection occurred unrelated to treatment, with no other primary safety events. The secondary outcome was to investigate efficacy based on improvement in corneal epithelial surface integrity (complete success) or improvement in corneal vascularization and/or participant symptomatology as measured by OSDI and SANDI (partial success). 86%, 93%, and 92% of grafts resulted in complete or partial success at 3, 12, and 18 months, respectively. Our results provide strong support that CALEC transplantation is safe and feasible and further studies are needed to evaluate therapeutic efficacy. Clinicaltrials.gov registration: NCT02592330.
Comments