A groundbreaking study published in The Lancet has showcased the safety and early efficacy of stem-cell-derived corneal implants in treating limbal stem cell deficiency (LSCD), a severe condition that causes vision impairment. This first-in-human trial offers hope for patients with limited treatment options, especially those unsuitable for traditional therapies like autologous or allogeneic corneal transplants.
The study conducted at Osaka University Hospital evaluated the use of induced pluripotent stem cell-derived corneal epithelial sheets (iCEPS) for treating moderate to severe LSCD in four adults aged 39 to 72. Developed by reprogramming human cells into iPSCs and differentiating them into corneal epithelial cells, the iCEPS were applied to the corneal surface after a keratectomy procedure. Over a 52-week period, followed by a year of safety monitoring, the results were promising, with no serious adverse events, tumor formation, or immunological rejection. Three patients showed significant clinical improvement, with marked reductions in LSCD severity, corneal epithelial defects, and visual acuity, while the fourth patient showed partial improvement. Quality of life improved for three participants, although the fourth patient experienced a decline. The severity of scar tissue (symblepharon) remained unchanged, and corneal opacification and neovascularization decreased in most patients.
LSCD arises when limbal stem cells, located at the edge of the cornea and essential for regenerating the corneal epithelium, are damaged or depleted. This leads to corneal surface deterioration, scarring, and significant visual impairment. Causes include trauma, immune-mediated diseases, and genetic disorders. Current treatments, which involve grafting healthy corneal tissue, face several challenges, such as immune rejection, donor scarcity, and inconsistent tissue quality. iCEPS represent a promising alternative, though their clinical use is still in early development. The use of iCEPS has several advantages, including the potential for personalized treatment using autologous cells, reducing the risk of immune rejection. These cells are transplanted onto the patient’s corneal surface after removing damaged tissue, helping to restore the corneal epithelium, improve vision, and reduce inflammation and scarring. iCEPS are particularly useful in cases where traditional treatments, such as corneal transplants, may not be effective due to the absence of viable limbal stem cells.
A review by Ghareeb et al. highlighted that the treatment of LSCD is a prime example of how advancements in basic science can be rapidly applied in surgical settings. They emphasized that bioengineering techniques enable the reconstruction of the stem cell niche’s physical properties, while induced pluripotent stem cells provide an unlimited source of autologous limbal stem cells.
The study confirms the safety of iCEPS and their potential to treat LSCD without HLA matching, reducing reliance on immunosuppressive therapies. This marks a significant advancement in regenerative medicine, offering a reliable alternative to donor corneal tissue. While one patient showed partial regression, further research is needed to assess long-term efficacy and immune response management. Larger trials are essential to validate these findings, but this pioneering trial positions stem-cell-derived corneal implants as a promising solution for restoring vision in LSCD patients.
References
- Soma T, Oie Y, Takayanagi H, Matsubara S, Yamada T, Nomura M, et al. Induced pluripotent stem-cell-derived corneal epithelium for transplant surgery: a single-arm, open-label, first-in-human interventional study in Japan. The Lancet. 2024 Nov 16;404(10466):1929–39.
- Ghareeb AE, Lako M, Figueiredo FC. Recent Advances in Stem Cell Therapy for Limbal Stem Cell Deficiency: A Narrative Review. Ophthalmol Ther. 2020 Dec 1;9(4):809–31.