MSC-encapsulated porous microparticle eye drops for autoimmune dry eye disease treatment in NOD mice.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40991713.
- Also identified by DOI 10.1126/sciadv.adu9772 and PMC identifier 12459467.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Dry eye disease (DED) is characterized by chronic inflammation and an unstable tear film. Stem cells have shown potential for DED treatment, but the main challenge lies in improving cell delivery effectiveness. Here, we developed eye drops for autoimmune DED treatment using porous arginine-glycine-aspartic acid (RGD)-modified alginate microcarriers with mesenchymal stem/stromal cells (MSCs) (RGD-Alg@MSCs). These microcarriers provided a favorable microenvironment for large-scale cell expansion while maintaining stemness with ideal mechanical properties for ocular application. In vitro, RGD-Alg@MSCs demonstrated significantly enhanced therapeutic effects compared to conventional MSCs, including improved cell viability, reduced apoptosis and reactive oxygen species, and enhanced release of immunomodulatory factors. Transcriptomic analysis revealed distinct molecular mechanisms underlying these enhanced therapeutic effects. In the mouse model, RGD-Alg@MSCs exhibited prolonged ocular retention and enhanced tear production, promoted corneal healing, and suppressed inflammation by inhibiting dendritic cell activation and T<sub>H</sub>17 differentiation. Our microcarrier system substantially improves stem cell delivery efficiency for treating autoimmune DED.
Medical subject headings
- Dry Eye Syndromes
- Mesenchymal Stem Cells
- Ophthalmic Solutions
- Mesenchymal Stem Cell Transplantation
- Autoimmune Diseases