Current Advancements in Corneal Cell-Based Therapy

Corneal epithelial stem cells (CEpSCs) mostly reside at the limbal area and are responsible for tissue homeostasis throughout life. Once complete CEpSC deficiency occurs, regenerative medicine cell-based therapy using CEpSCs or their alternatives can provide successful clinical outcomes. Due to an improved understanding of CEpSCs and mucosal epithelial stem cells, major advancements have been made over the past few decades in in vivo and ex vivo cell-based ocular surface reconstruction therapies for the treatment of severe ocular surface diseases. New therapeutic concepts and clinical strategies are emerging for the treatment of corneal endothelial dysfunction. For example, unlike corneal epithelial cells, in vivo corneal endothelial cells (CECs) stop proliferating and are arrested in the G1 phase of the cell cycle due to cell-to-cell contact inhibition and exposure to a high concentration of transforming growth factor-beta in the aqueous humor. Thus, the production of CECs with good functionality in culture has consistently been difficult. To solve this problem, Rho-associated protein kinase inhibition has taken center stage, as it not only makes the production of human CECs in culture closely mimic the functional characteristics of in vivo healthy CECs possible but also helps sustain those biological properties. Thus, cultured human CEC injection therapy is now moving to the forefront for the treatment of corneal endothelial failure. Herein, we summarize key historical discoveries in corneal cell-based regenerative medicine and illustrate the concept of corneal cell therapy for the treatment of refractory corneal epithelial and endothelial diseases.