Revisiting Existing Evidence of Corneal Endothelial Progenitors and Their Potential Therapeutic Applications in Corneal Endothelial Dysfunction

Purpose: A recent successful clinical trial demonstrated that a less invasive cell-injection procedure is a viable medical modality for treating corneal endothelial dystrophy. This medical advance still relies on human corneal endothelial cell (HCEC) sources derived from rare cornea donations. The progenitor of the corneal endothelium, which has the characteristics of active proliferation and lineage restriction, will be an ideal cell source for expansion ex vivo. However, the distribution of progenitor-like cells in the corneal endothelial sheet has been under debate for more than a decade. Methods: This paper re-examines the scientific evidence of the existence of human corneal endothelial progenitors (HCEPs) from the aspects of (1) the origin of cornea formation during ocular development, (2) manifestations from clinical studies, and (3) the distinctive properties of ex vivo-cultured subpopulations. Results: The discrepancies regarding different types of progenitor-like cells in various locations of the cornea are based on the fact that the corneal endothelium is derived from different cell types with multiple origins during corneal formation. Conclusions: Resolving this long-standing issue in corneal biology will enable various types of progenitors to be isolated and their potencies regarding the formation of functional endothelial cells to be examined. Additionally, an effective niche system for quantitatively producing therapeutic cells can be formulated to satisfy the burning need associated with corneal endothelial dystrophy in the future.