A Powerful Tool in the Treatment of Myocardial Ischemia-Reperfusion Injury: Natural and Nanoscale Modified Small Extracellular Vesicles Derived from Mesenchymal Stem Cells

Zhou Zhou,1,2,* Xuan Zhang,1,* Shuai Wang,1 Xianliang Wang,1 Jingyuan Mao1 1Cardiovascular Department, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine/National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, People’s Republic of China; 2Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xianliang Wang; Jingyuan Mao, Email xlwang1981@126.com; jymao@126.comAbstract: Myocardial ischemia-reperfusion injury (MI/RI) constitutes a pivotal determinant impacting the long-term prognosis of individuals afflicted by ischemic cardiomyopathy subsequent to reperfusion therapy. Stem cells have garnered extensive application within the realm of MI/RI investigation, yielding tangible outcomes. Stem cell therapy encounters certain challenges in its application owing to the complexities associated with stem cell acquisition, a diminished homing rate, and a brief in vivo lifespan. Small extracellular vesicles (sEV) originating from mesenchymal stem cells (MSCs) have been demonstrated to possess the benefits of abundant availability, reduced immunogenicity, and a diminished tumorigenic incidence. They can exert their effects on damaged organs, improving injuries by transporting a lot of constituents, including proteins, RNA, lipid droplets, and more. This phenomenon has garnered substantial attention in the context of MI/RI treatment. Simultaneously, MSC-derived sEV (MSC-sEV) can exhibit enhanced therapeutic advantages through bioengineering modifications, biomaterial incorporation, and natural drug interventions. Within this discourse, we shall appraise the utilization of MSC-sEV and their derivatives in the context of MI/RI treatment, aiming to offer valuable insights for future research endeavors related to MI/RI.Keywords: myocardial ischemia-reperfusion injury, mesenchymal stem cells, small extracellular vesicles, nanoscale modification, natural drug