Regenerative Cell Therapy for Corneal Endothelium

Abstract

Endothelial cell dysfunction as in Fuchs dystrophy or pseudophakic bullous keratopathy, and the limited regenerative capacity of human corneal endothelial cells (HCECs), drive the need for corneal transplant. In response to limited donor corneal availability, significant effort has been directed towards cell therapy as an alternative to surgery. Stimulation of endogenous progenitors, or transplant of stem cell-derived HCECs or in vitro-expanded, donor-derived HCECs could replace traditional surgery with regenerative therapy. Ex vivo expansion of HCECs is technically challenging, and the basis for molecular identification of functional HCECs is not established. Delivery of cells to the inner layer of the human cornea is another challenge: different techniques, from simple injection to artificial corneal scaffolds, are being investigated. Despite remaining questions, corneal endothelial cell therapies, translated to the clinic, represent the future for the treatment of corneal endotheliopathies.

Keywords: Cell therapy; Corneal endothelial dysfunction; Corneal endothelium; Corneal transplant; Endothelial regeneration; Endotheliopathies; Human corneal endothelial cell replacement therapy; Human corneal endothelial cells; Magnetic cell delivery; Magnetic corneal endothelial cells; Regenerative medicine; Stem cells.

FIGURE 1

(A) Cultured in vitro, HCECs maintain their characteristic cobblestone-like morphology in early passages. (B) With increased number of passages, HCECs lose their characteristic morphology, undergo endothelial-mesenchymal transition (EnMT), and become fibroblastic.