Abstract 12290: Exosomal miR-223 Contributes to Mesenchymal Stem Cell-Elicited Cardio-protection in Polymicrobial Sepsis

• DOI: 10.1161/circ.132.suppl_3.12290
• Publication Date: 2024-04-23T10:56:22Z
• Authors: Xiaohong Wang; Wei Huang; Yigang Wang; Guo-Chang Fan

Background: Mesenchymal stem cells (MSCs) have been shown to elicit cardioprotective effects in polymicrobial sepsis induced by cecal ligation and puncture (CLP). However, the underlying mechanisms remain obscure. While recent studies indicated that miR-223 is highly enriched MSC-derived exosomes, whether exosomal contributes MSC-mediated cardioprotection unknown. Methods Results: MSCs harvested from bone marrow of female pre-miR-223 knockout (KO) wild-type (WT) mice were injected into male WT via tail vein 1 h after CLP. We observed mortality at 32h post-CLP was significantly reduced WT- MSC-injected mice, but not KO-MSC-treated groups, compared with controls. CLP-triggered cardiac dysfunction, apoptosis inflammatory response also attenuated treated WT-MSCs, KO-MSCs. Furthermore, vitro study showed WT-MSCs could release miR-223-enrinched exosomes (WT-exosomes) taken up macrophages cardiomyocytes, leading production pro-inflammatory factors (TNF-α, IL-1β, IL-6) cardiomyocyte death upon LPS insults. By contrast, miR-223-KO-exosomes stimulated macrophage these cytokines increased challenge. In vivo injection KO-exosomes 1h increased: 1) serum levels TNF-α, IL-6; 2) dysfunction; 3) animal mortality. Conversely, treatment WT-exosomes displayed opposite effects. Mechanistically, we identified miR-223-KO contained higher Sema3A Stat3, two known targets (5p & 3p), than WT-exosomes. Accordingly, proteins able be transferred inflammation cell death. encased miR-223, which delivered resulting down-regulation Stat3. Conclusions: These data for first time indicate plays an essential role MSC-induced sepsis.