Safety and efficacy of human ESC-derived corneal endothelial cells for corneal endothelial dysfunction

Abstract

Abstract Background Research on human pluripotent stem cells (hPSCs) has shown tremendous progress in cell-based regenerative medicine. Corneal endothelial dysfunction is associated with the loss and degeneration of corneal endothelial cells (CECs), rendering cell replacement a promising therapeutic strategy. However, comprehensive preclinical assessments of hPSC-derived CECs for this cell therapy remain a challenge. Results Here we defined an adapted differentiation protocol to generate CECs consistently and efficiently from clinical-grade human embryonic stem cells (hESCs) with xeno-free medium and manufactured cryopreserved CECs. Cells express high levels of typical CEC markers and exhibit transendothelial potential properties in vitro typical of CECs. After rigorous quality control measures, cells meeting all release criteria were available for in vivo studies. We found that there was no overgrowth or tumorigenicity of grafts in immunodeficient mice. After grafting into rabbit models, the surviving CECs ameliorated edema and recovered corneal opacity. Conclusions Our work provides an efficient approach for generating CECs and demonstrates the safety and efficacy of CECs in disease modeling. Therefore, clinical-grade hESC-derived CECs are a reliable source for future clinical treatment of corneal endothelial dysfunction.