Exosomes from Human iPSC-Derived Retinal Organoids Enhance Corneal Epithelial Wound Healing

Area of Science:

• Ophthalmology
• Regenerative Medicine
• Cell Biology

Background:

• Corneal epithelial wound healing is crucial for maintaining ocular surface integrity.
• Current treatments for corneal wounds have limitations.
• Exosomes derived from stem cells show potential in tissue regeneration.

Purpose of the Study:

• To investigate the therapeutic efficacy of exosomes derived from human-induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs) in promoting corneal epithelial wound healing.
• To elucidate the underlying molecular mechanisms of exosome-mediated corneal healing.

Main Methods:

• Isolation and characterization of exosomes from hiPSC-derived ROs (Exo-ROs) using ultracentrifugation, nanoparticle tracking analysis, and transmission electron microscopy.
• Topical application of Exo-ROs in a murine model of corneal epithelial wounds.
• Assessment of wound closure, cell proliferation (5-ethynyl-2'-deoxyuridine assay), inflammatory markers (qRT-PCR), and molecular pathways (RNA sequencing, microRNA analysis).

Main Results:

• Exo-RO treatment significantly enhanced corneal wound closure at 24 hours post-injury compared to controls.
• Increased cell proliferation and decreased inflammatory markers were observed in the Exo-RO treated group.
• RNA sequencing revealed that Exo-ROs target PI3K-Akt, TNF, MAPK, and IL-17 signaling pathways, and modulate retinoic acid and eicosanoid metabolism.

Conclusions:

• hiPSC-derived RO exosomes demonstrate significant therapeutic potential for accelerating corneal epithelial wound healing.
• Exo-ROs promote healing by enhancing cell proliferation and modulating inflammatory and metabolic pathways.
• These findings suggest Exo-ROs as promising novel therapeutic agents for corneal regeneration.