A Randomized Controlled Trial of Cultivated Limbal Epithelial Cells Compared to Mesenchymal Stem Cells for the Treatment of Corneal Failure due to Limbal Stem Cell Deficiency

Abstract

Purpose : Ocular stem cell transplantation derived from donor corneoscleral junction is a functional cell therapy to correct limbal stem cell deficiencies that lead to corneal blinding. Mesenchymal stem cells have been properly tested in animal models of this ophthalmic pathology, but never in human eyes despite the multiple advantages over limbal epithelial cells.

Methods : We conducted a 6- to 12-month randomized, double-masked trial with the hypothesis that bone marrow-derived mesenchymal stem cell transplantation (MSCT) is safe and equally efficient as cultivated limbal epithelial transplantation (CLET) in the management of epithelial recovery in corneas damaged due to limbal epithelial stem cell deficiency. Both cell types were cultured on human amniotic membrane. Primary endpoints included a combination of symptoms, clinical signs, and the objective improvement of the epithelial phenotype in the central cornea by in vivo confocal microscopy.

Results : We included 28 transplants, 11 randomized to CLET and 17 to MSCT. Global success at 6 and 12 months was achieved by 72.7% and 77.8% of CLET cases and by 76.5% and 85.7% of MSCT cases, respectively (no significant differences). Improvement of epithelial phenotype in central cornea at 12 months occurred in 55.6% and 71.4% of CLET and MSCT cases, respectively (no significant difference). There were no serious adverse events related with transplants or medications. Thus, MSCT was safe and as efficacious as CLET.

Conclusions : Our evidence-based approach showed that mesenchymal stem cells transplanted to the ocular surface facilitated recovery of a potentially blinding epithelial pathology due to limbal stem cell deficiency. Since MSCT is more efficient in terms of patient morbidity, time- and resource-consumption, and economic expenditure than CLET, MSCT translation into clinical practice should be pursued. (ClinicalTrials.gov number, NCT01562002.)

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.