Researchers led by Osaka University in Japan have conducted the first human trial using induced pluripotent stem-cell-derived corneal epithelium to treat limbal stem cell deficiency, offering a potential new avenue for restoring vision.

Limbal stem cell deficiency (LSCD) is a severe ocular condition where the loss of functioning adult stem cells at the cornea’s edge leads to vision impairment due to the invasion of fibrotic conjunctival tissue over the cornea. Limbal stem cells normally perform repair functions by differentiating into corneal epithelium. Without them, the integrity and transparency of the corneal surface becomes compromised, leading to fibrotic tissue buildup, and ultimately, vision loss.

Traditional treatments often involve grafts from the patient’s healthy eye or donors, but these methods carry risks like immunological rejection, or require the removal of healthy tissue.

In a study titled “Induced pluripotent stem-cell-derived corneal epithelium for transplant surgery: a single-arm, open-label, first-in-human interventional study in Japan,” published in The Lancet, researchers conducted transplants of pluripotent stem cell (iPSC)-derived corneal epithelial sheets (iCEPS) as a potential treatment for LSCD.

Four patients with LSCD participated in the study. After removing any fibrotic tissue, the team transplanted allogeneic iCEPS onto the affected eyes. All surgeries were performed without human leukocyte antigen (HLA) matching. Half the patients received low-dose cyclosporine (typically used to mitigate organ rejection after a transplant), while the other half received no immunosuppressive agents beyond corticosteroids.

Two years of monitoring revealed no severe adverse events. Minor adverse events were managed effectively and without lasting effects.

All four patients experienced significant improvements in vision. Disease stages advanced to less severe classifications in three patients. One patient, with a more severe underlying condition, initially improved to a less severe stage by 32 weeks, but later regressed to baseline after one year. Quality-of-life assessments aligned with visual improvements, with three of the four patients reporting enhanced scores.

Overall, the study demonstrated that iCEPS transplantation not only stabilizes the corneal surface but also restores functional vision, significantly enhancing the daily lives of patients with limbal stem cell deficiency. Beneficial outcomes were more pronounced in patients who received low-dose cyclosporine, suggesting that non-use might have triggered subclinical immunological rejection.

The iCEPS were cultivated using a method that replicates aspects of natural eye development to produce functional corneal cells. This technique not only ensures the structural integrity of the grafts but also reduces immunogenicity, potentially eliminating the need for HLA matching and extensive immunosuppression typically required in traditional grafts.

The successful result is a major therapeutic advancement, building on earlier successes in regenerative medicine while overcoming the limitations of existing LSCD surgical treatments. The Osaka team plans to initiate a larger multicenter clinical trial to further validate the findings and explore the broader applicability of iCEPS transplantation.

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