Therapeutic Delivery of Bone Marrow Mesenchymal Stem Cell-Derived Exosomal miR-143-3p Inhibits Myocardial and Systemic Inflammation and Attenuates Sepsis-Related Myocardial Injury.

Authors

Yuyang Qiu, Lian Liao, Tian Zhang, Yiming Ma, Jianyu Fu, Jiakai Wang, Xu Liu, Wei Xie

Published in

Inflammation. Jul 10, 2026. Epub Jul 10, 2026.

Abstract

Sepsis-related myocardial injury (SRMI) is a major contributor to mortality in septic patients, driven by uncontrolled inflammation and macrophage dysregulation. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) possess immunomodulatory properties, but their cardioprotective mechanisms remain unclear. Here, we investigated whether BMSC-Exos deliver microRNA-143-3p (miR-143-3p) to reprogram macrophages and attenuate SRMI. Exosomes were isolated from murine bone marrow mesenchymal stem cells and characterized by electron microscopy, nanoparticle tracking analysis, and immunoblotting. In lipopolysaccharide-stimulated macrophages, BMSC-Exos promoted a shift from pro-inflammatory M1 to reparative M2 polarization, and reduced pro-inflammatory cytokine secretion. In a mouse model of endotoxemia, BMSC-Exo administration improved seven-day survival, preserved cardiac function, decreased circulating myocardial injury markers, and increased the proportion of cardiac M2 macrophages. MicroRNA sequencing identified miR-143-3p as highly enriched in BMSC-Exos but downregulated in circulating exosomes from septic mice. Delivery of miR-143-3p mimics recapitulated the protective effects of BMSC-Exos, while inhibition of miR-143-3p exacerbated injury. Mechanistically, miR-143-3p directly targeted Toll-like receptor 4 (TLR4) and suppressed the downstream myeloid differentiation primary response 88/nuclear factor-κB (MyD88/NF-κB) signaling pathway. Furthermore, TLR4 knockdown phenocopied the anti-inflammatory and M2-polarizing effects of miR-143-3p. These findings indicate that BMSC-Exos attenuate SRMI by transferring miR-143-3p to macrophages, where it inhibits TLR4/MyD88/NF-κB signaling and promotes M2 polarization, highlighting a potential therapeutic strategy for septic cardiac injury.

PMID:
42430016
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.