Emerging strategies in corneal Regeneration: The role of induced pluripotent stem cell-based therapies

Corneal opacity remains a leading cause of global blindness, yet conventional corneal transplantation is constrained by donor scarcity, surgical limitations, and suboptimal long-term outcomes. In response, regenerative strategies are advancing to restore structural and functional integrity across all three corneal layers—epithelium, stroma, and endothelium—through cell-based and bioengineered therapies. Among these, induced pluripotent stem cells (iPSCs) have emerged as a versatile and scalable source capable of generating corneal-like cells under defined, xeno-free conditions. This review provides a concise summary of recent clinical progress in corneal cell therapy and tissue engineering, while placing major emphasis on systematically updating preclinical advances in iPSC-based corneal regeneration. Additionally, we highlight the only two first-in-human trials employing iPSC-derived corneal cells, which demonstrate encouraging early safety and efficacy outcomes, yet underscore critical translational challenges including tumorigenicity, immunogenicity, and heterogeneity. Emerging solutions—such as HLA-matched iPSC banks, gene editing, and naïve-state reprogramming—are discussed as key strategies to enhance clinical readiness and scalability.