Limbal Epithelial Stem Cell Transplantation: a Phase II Multicenter Trial

This project aims to conduct a multicenter, single-arm phase II study, in which we will assess the safety and efficacy of transplanting standardized, non-xenogenic limbal stem cell grafts for patients with LSCD. The Good Manufacturing Practice (GMP) clean room facilities at the Centre for Cell Therapy and Regenerative Medicine (CCRG, UZA) will conduct tissue engineering, while the Departments of Ophthalmology at the University Hospitals in Antwerp (UZA), Brussels (UZB) and Gent (UZG) will enrol patients, perform pre-operative tests, harvest the limbal biopsies, perform the auto- or allogenic graft transplantation and follow-up. Based on the past experience from our phase I/II mono-centre human clinical trial, we have been able to document the safety and feasibility of the transplantation. 12/18 patients (2/3 allogenic and 10/15 autologous) have shown decrease in corneal vascularization, complete epithelialization and incorporation of the graft into the anterior cornea post limbal stem cell transplantation. However our current results are limited with respect to the sample size, feasibility of allogenic transplantation (only 3 cases), long term follow-up (mean of 22 months, range 4-43 months) and disease monitoring strategies. Longer patient follow-up to determine long term success (especially following subsequent corneal transplants) and inclusion of a larger allogenic patient population need to be addressed before this treatment can be translated to the clinics and recognized by the RIZIV as a reimbursable cell therapy.

It is pertinent to say that this cell based therapy has the potential to provide this orphan pathology with an effective treatment option. The Flemish society will benefit from this project by improved rehabilitation of patients suffering from corneal blindness due to LSCD. By providing this treatment option we can offer a ray of hope to patients that would formerly have to learn to live with their disability. By restoring vision for these patients it is possible to reintegrate them into society as socially accepted individuals. Even a small degree of visual rehabilitation can make all the difference. For example, a slight increase in visual acuity can restore a person's ability to drive rather than having them rely exclusively on public transportation. More independence and a better quality of life are the main objectives that we are striving to achieve as the major outcome of this project.

Inclusion criteria

• Adults ≥ 18 years
• Voluntary written informed consent
• Patients suffering from LSCD IIa and IIb. Those suffering from IIc may be included once inflammation has subsided and cornea can be staged as IIb.
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
• Women of child-bearing potential should use adequate contraception prior to study entry and for the duration of study participation. Negative serum or urine β-HCG pregnancy test at screening.

Exclusion criteria

• Subjects who are pregnant or lactating
• Subjects who have sensitivity to drugs that provide local anesthesia
• Subjects suffering from active infection of the external eye
• Medical conditions that prohibit the use of systemic immunosuppression (in cases of allogenic transplantation)