Mesenchymal stem cell-derived extracellular vesicles for dry eye disease: principles, progress, and challenges

Area of Science:

• Ophthalmology and Regenerative Medicine

Background:

• Dry eye disease (DED) is a prevalent ocular surface disorder with significant public health impact.
• Ocular surface inflammation plays a central role in DED pathogenesis.
• Current DED treatments face limitations, necessitating novel therapeutic approaches.

Purpose of the Study:

• To review the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) for DED.
• To evaluate preclinical advances and translational challenges of MSC-EV therapy for DED.
• To highlight strategies for optimizing MSC-EV therapeutic performance.

Main Methods:

• Comprehensive literature review focusing on DED pathogenesis and MSC-EV therapy.
• Evaluation of MSC-EV properties, advantages, and optimization strategies.
• Assessment of advanced preclinical models, including 3D ocular surface and ex vivo models.
• Analysis of translational challenges and regulatory considerations.

Main Results:

• MSC-EVs possess anti-inflammatory, immunomodulatory, and regenerative properties beneficial for DED.
• Advantages of MSC-EVs include cell-free nature, low immunogenicity, and suitability for topical delivery.
• Advanced strategies like cargo engineering and biomaterial-assisted delivery can enhance MSC-EV efficacy.
• Umbilical cord-derived MSC-EVs show significant potential for clinical translation.

Conclusions:

• MSC-EVs represent a promising, potentially transformative therapy for refractory DED.
• Optimization strategies can improve targeted delivery, retention, and immunomodulation of MSC-EVs.
• Overcoming challenges related to ocular barriers, standardization, safety, and regulation is crucial for clinical success.
• Further validation in human-relevant models and clinical studies is essential.