Human amniotic epithelial cell-derived extracellular vesicles provide an extracellular matrix-based microenvironment for corneal injury repair.

Abstract

To study the biological functions and applications of human amniotic epithelial cell-derived extracellular vesicles (hAEC-EVs), the cargos of hAEC-EVs were analyzed using miRNA sequencing and proteomics analysis. The hAECs and hAEC-EVs in this study had specific characteristics. Multi-omics analyses showed that extracellular matrix (ECM) reorganization, inhibition of excessive myofibroblasts, and promotion of target cell adhesion to the ECM were their primary functions. We evaluated the application of hAEC-EVs for corneal alkali burn healing in rabbits and elucidated the fundamental mechanisms. Slit-lamp images revealed that corneal alkali burns induced central epithelial loss, stromal haze, iris, and pupil obscurity in rabbits. Slit-lamp examination and histological findings indicated that hAEC-EVs facilitated re-epithelialization of the cornea after alkali burns, reduced scar formation and promoted the restoration of corneal tissue transparency. Significantly fewer α-SMA-positive myofibroblasts were observed in the hAEC-EV-treated group than the PBS group. HAEC-EVs effectively promoted the proliferation and migration of hCECs and hCSCs in vitro and activated the focal adhesion signaling pathway. We demonstrated that hAEC-EVs were excellent cell-free candidates for the treatment of ECM lesion-based diseases, including corneal alkali burns. HAEC-EVs promoted ECM reorganization and cell adhesion of target tissues or cells via orderly activation of the focal adhesion signaling pathway.