Exosomal MicroRNA-223 Contributes to Mesenchymal Stem Cell-Elicited Cardioprotection in Sepsis

Scientists at the University of Cincinnati College of Medicine, together with colleagues, have shown that the cardio-protective effects known to be associated with mesenchymal stem cells (MSCs) during sepsis are likely attributable, at least in part, to the high levels of microRNA-223 (miR-223) know to exist in MSC-derived exosomes that may reach the heart. According to the authors, their data indicates, for the first time, that exosomal miR-223 plays an essential role in MSC-induced cardio-protection in sepsis. The new work was published online on September 8, 2015 in an open-access article in Scientific Reports. The article is titled “Exosomal miR-223 Contributes to Mesenchymal Stem Cell-Elicited Cardioprotection in Polymicrobial Sepsis.” In a mouse model of sepsis, the scientists showed that injection of MSCs from which miR-223 had been eliminated (miR-223-KO MSCs), did not confer protection against the sepsis-triggered cardiac dysfunction, apoptosis, and inflammatory response in the model mice. However, wild-type MSCs (WT-MSCs) were able to provide protection that was associated with exosome release. Next, the scientists showed that treatment of sepsis-model mice with exosomes released from miR-223-KO MSCs significantly exaggerated sepsis-induced injury. On the other hand, treatment with WT-MSC-derived-exosomes displayed protective effects. The scientists then determined that miR-223-KO MSC-derived exosomes contained higher levels of Sema3A and Stat3, two known protein targets of miR-223 (5p & 3p), than were contained in WT-MSC-derived exosomes. Accordingly, these exosomal proteins from miR-223-KO MSC-derived exosomes were transferred to cardiomyocytes, leading to increased inflammation and cell death.
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