Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a serious condition with few treatment options and a poor outlook. Mesenchymal stem cell-derived microvesicles (MSCs-MVs) offer a potential cell-free therapy, but their effectiveness and the role of their miRNA content in RA-ILD are not well understood.

Objectives: This study aims to investigate the therapeutic potential and mechanisms of MSCs-MVs in a preclinical RA-ILD model, offering new insights and a promising treatment strategy for this condition.

Methods: A comorbid RA-ILD mouse model was created using collagen-induced arthritis and bleomycin-induced pulmonary fibrosis. Mice received high- or low-dose MSCs-MVs via tail vein injection. The treatment’s effectiveness was evaluated by assessing arthritis severity and pulmonary fibrosis through clinical scores, imaging, histopathology, lung function, and Lung Coefficient. Lung fibrotic markers were measured using immunohistochemistry and Western Blot. Small RNA sequencing of MSCs-MVs was conducted to explore the underlying mechanism.

Results: Administering MSCs-MVs significantly reduced arthritis and pulmonary fibrosis severity. Treated mice showed better joint and lung scores, with decreased fibrotic areas and lower levels of fibrotic proteins like anti-α-smooth muscle actin, collagen I, and fibronectin. Small RNA sequencing indicated that MSCs-MVs contain microRNAs (miRNAs) (e.g., miR-148a-3p) targeting critical pathways in RA-ILD, such as transforming growth factor-β (TGF-β) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling.

Conclusions: Our research illustrates that MSCs-MVs exhibit a significant protective effect against RA-ILD in a comorbid model. This protective effect is likely facilitated by the transfer of specific miRNAs that modulate essential profibrotic and inflammatory pathways. These results underscore the therapeutic potential of MSCs-MVs as an innovative cell-free approach for RA-ILD treatment and identify miRNA-mediated pathway regulation as a pivotal mechanism.

Figure 1.

Evaluation of MSC-MVs effects on arthritis and joint degeneration in mice with rheumatoid interstitial lung disease in RA-ILD Mice

Figure 2.

Evaluation of the therapeutic effects of MSC-MVs on lung tissue and function in RA-ILD mice

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.