A recent study detailed the first human trial of induced pluripotent stem cell-derived corneal epithelium to treat limbal stem cell deficiency, a condition that leads to vision loss due to the depletion of corneal epithelial cells.

Conducted at Osaka University Hospital, the study involved four patients with severe limbal stem cell deficiency (LSCD) who received grafts of induced pluripotent stem cell (iPSC)-derived corneal epithelial cell sheets (iCEPS) without human leukocyte antigen matching. Two patients also received low-dose cyclosporine while the other two did not. The primary outcome was safety, measured by adverse events, as the abstract explained. These events were monitored for two years.

“A unilateral LSCD is often associated with acquired non-immune-mediated aetiologies such as trauma to the eye caused by thermal or chemical burns,” the researchers described in their article in The Lancet. “Bilateral LSCDs can be caused by acquired primary immune-mediated aetiologies…or idiopathic or hereditary disease such as congenital aniridia.”

While existing therapies—such as autologous transplant procedures for unilateral LSCD and allogeneic cultivated limbal epithelial cell transplantation for bilateral LSCD—have value, autologous cell sources require a biopsy and “postoperative neovascularization following cultivated oral mucosal epithelial cell sheet transplantation is inevitable, variable in its severity, and very difficult to manage,” the investigators wrote. Allogenic therapies carry the risk of rejection. Therefore, the researchers developed the protocol which “effectively produces precursor cells of ocular tissues from human iPSCs.”

Patient outcomes varied. While patients with milder LSCD experienced stable improvements, the patient with more severe disease (due to toxic epidermal necrolysis) saw some regression, potentially due to mild immunological response. By 52 weeks, all patients exhibited reduced corneal opacity, improved LSCD staging, and enhanced corrected distance visual acuity. Three patients maintained these gains for the entire follow-up period. Over two years, no cases of tumor formation or clinical rejection were reported.

The investigators hypothesized two possible mechanisms of action for iCEPS' ability to recover the corneal surface:

1. Regenerated corneal cells may be derived from cells within iCEPS
2. iCEPS may be replaced by host conjunctival epithelial cells through conjunctival transdifferentiation

They did not conduct genotyping to find out whether the transplanted iPSC-derived cells remained in patients' corneas in an effort to avoid further ocular trauma, but they plan to initiate a multi-center trial to further explore the efficacy of iCEPS on LSCD in a larger population.

A full list of author disclosures can be found in the published research.