Advances in Differentiation of Induced Pluripotent Stem Cell–Derived Corneal Endothelial Cells

Corneal endothelial cells lack the ability to regenerate, and their dysfunction is a major cause of corneal blindness worldwide, yet treatment is limited by the scarcity of donor tissue. The emergence of stem cell technology has generated opportunities to generate corneal endothelial cells as a renewable and patient-specific source of therapy. Over the past decade, several protocols have been developed to direct the differentiation from pluripotent stem cells to corneal endothelial cells, but their efficiency and reproducibility vary considerably. This review examines the signaling pathways that influence the transition to corneal endothelial identity, with particular focus on transforming growth factor β, bone morphogenetic protein, and WNT signaling, as well as other modulators implicated in corneal development. In addition, the review evaluates the methods used to characterize corneal endothelial cell identity, comparing research-focused approaches with clinically applicable standards. By integrating pathway biology, methodologic assessment, and comparative analysis, this review aims to provide a clear perspective on the current state of induced pluripotent stem cell-derived corneal endothelial cell research and to support the advancement of strategies that may eventually lead to clinical translation.