作者： Jinli Wang^ab，Christine J.Lee^a，Michael B.Deci^a，Natalie Jasiewicz^e，Anjali Verma^e，John MCanty^cd，Juliane Nguyen^e

^a Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, USA

^b Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, NY, USA

^c Department of Medicine, Department of Physiology and Biophysics, Department of Biomedical Engineering, The Clinical and Translational Research Center of the University at Buffalo, Buffalo, NY, USA

^d VA Western New York Healthcare System, Buffalo, NY, USA

^e Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

摘要：Myocardial infarction (MI) remains a major cause of mortality worldwide. Despite significant advances in MI treatment, many who survive the acute event are at high risk of chronic cardiac morbidity. Here we developed a cell-free therapeutic that capitalizes on the antifibrotic effects of micro(mi)RNA-101a and exploits the multi-faceted regenerative activity of mesenchymal stem cell (MSC) extracellular nanovesicles (eNVs). While the majority of MSC eNVs require local delivery via intramyocardial injection to exert therapeutic efficacy, we have developed MSC eNVs that can be administered in a minimally invasive manner, all while remaining therapeutically active. When loaded with miR-101a, MSC eNVs substantially decreased infarct size (9.2 ± 1.7% vs. 20.0 ± 6.5%) and increased ejection fraction (53.6 ± 7.6% vs. 40.3 ± 6.0%) and fractional shortening (23.6 ± 4.3% vs. 16.6 ± 3.0%) compared to control. These findings are significant as they represent an advance in the development of minimally invasive cardio-therapies.