Extracellular Vesicles From Adipose Stem Cells Prevent Muscle Damage and Inflammation in a Mouse Model of Hind Limb Ischemia: Role of Neuregulin-1

Objectives: Critical hindlimb ischemia is a severe consequence of peripheral artery disease. Surgical treatment does not prevent skeletal muscle impairment or improve long-term patient outcomes. The present study investigates the protective/regenerative potential and the mechanism of action of adipose stem cell-derived extracellular vesicles (ASC-EVs) in a mouse model of hindlimb ischemia. Approach and Results: We demonstrated that ASC-EVs exert a protective effect on muscle damage by acting both on tissue microvessels and muscle cells. The genes involved in muscle regeneration were up-regulated in the ischemic muscles of ASC-EV-treated animals. MyoD expression has also been confirmed in satellite cells. This was followed by a reduction in muscle function impairment in vivo. ASC-EVs drive myoblast proliferation and differentiation in the in vitro ischemia/reoxygenation model. Moreover, ASC-EVs have shown an anti-apoptotic effect both in vitro and in vivo. Transcriptomic analyses have revealed that ASC-EVs carry a variety of pro-angiogenic mRNAs, while proteomic analyses have demonstrated an enrichment of NRG1 (neuregulin 1). A NRG1 blocking antibody used in vivo demonstrated that NRG1 is relevant to ASC-EV-induced muscle protection, vascular growth, and recruitment of inflammatory cells. Finally, bioinformatic analyses on 18 molecules that were commonly detected in ASC-EVs, including mRNAs and proteins, confirmed the enrichment of pathways involved in vascular growth and muscle regeneration/protection. Conclusions: This study demonstrates that ASC-EVs display pro-angiogenic and skeletal muscle protective properties that are associated with their NRG1/mRNA cargo. We, therefore, propose that ASC-EVs are a useful tool for therapeutic angiogenesis and muscle protection

Degradation of mechanical properties of vinylester and carbon fiber/vinylester composites due to environmental exposure

An experimental investigation was undertaken to determine the effects of marine environmental exposure on the mechanical properties of vinylester resins (VE510A and VE8084) and carbon fiber/VE510A vinylester composites. The effect of carbon fiber sizing on the composite strengths was also examined. Neat resins were exposed to marine environments until moisture content reached a point of saturation after which they were tested in tension, compression and shear. Compared to the baseline dry specimens, specimens subjected to moisture showed overall increased ductility and a reduction in strength. Dry and moisture saturated composite specimens were tested in tension and compression in different orientations. Longitudinal specimens were tested in in-plane shear and interlaminar shear. Composites with F-sized carbon fibers displayed overall higher strength than those with G-sized fibers at both dry and moisture saturated conditions. An analysis of moisture absorption of the composites was performed which shows that the moisture up-take is dominated by the fiber/matrix region which absorbs up to 90% of the moisture. The composites experienced reduced strength after moisture absorption. The results revealed that the fiber sizing has stronger effect on the fiber/matrix interface dominated strengths than moisture up-take