Long-term observation and sequencing analysis of SKPs-derived corneal endothelial cell-like cells for treating corneal endothelial dysfunction

Background Corneal endothelial dysfunction is a principal cause of visual deficiency. Corneal transplantation is the most effective treatment for corneal endothelial dysfunction. However, a severe shortage of available donor corneas or human corneal endothelial cells (HCEC) remains a global challenge. Previously, we acquired corneal endothelial cell-like cells (CEC-like cells) derived from human skin-derived precursors (SKPs). CEC-like cells were injected into rabbit and monkey corneal endothelial dysfunction models and exerted excellent therapeutic effect. Method We prolonged the clinical observation in the monkey experiment for 2 years. PCR and DNA sequencing were carried out to confirm the existence of CEC-like cells. Histological examinations were carried out to show the corneal morphology. Further transcriptome sequencing was also carried out on HCEC, CEC-like cells before transplantation and after transplantation. Results The monkeys cornea remained transparent and normal thickness. The total endothelial cell density decreased gradually, but tended to be stable and remained in a normal range during 2-year observation. The CEC-like cells persist during observation and could adapt to the microenvironment after transplantation. The gene expression pattern of CEC-like cells was similar to HCEC and changed slightly after transplantation. Conclusions CEC-like cells could adapt to the microenvironment and had a good therapeutic effect after being transplanted into the monkey endothelial dysfunction model during long-term observation. This study provided a promising prospect of cell-based therapy for corneal endothelial dysfunction and may be clinically applied in regenerative medicine in the future.