Artificial cell derived vesicles from Ginsenoside Rg1-primed mesenchymal stromal cells mitigate oxidative stress and DNA damage in myocardial ischemic/reperfusion injury

Myocardial ischemia/reperfusion injury (MI/RI) remains a major challenge in the treatment of acute myocardial infarction due to the lack of effective therapeutic options. While mesenchymal stromal cells (MSCs) and their derivates show promising potential for MI/RI therapy, their clinical application is hindered by low transplantation efficiency and insufficient yield. In this study, we engineered nanoscale artificial cell-derived vesicles (ACDVs) by extruding Ginsenoside Rg1-primed MSCs (Rg1-MSCs), resulting in Rg1-ACDVs. Rg1-ACDVs displayed superior therapeutic efficacy compared to non-primed ACDVs and extracellular vesicles derived from Rg1-MSCs (Rg1-EVs). Multi-omics analysis revealed that Rg1-ACDVs possess distinct molecular signatures associated with promoting cell cycle progression and reducing DNA damage. These findings were further validated experimentally, demonstrating that Rg1-ACDVs effectively reduce reactive oxygen species (ROS) accumulation and mitigate DNA damage both in vitro and in vivo. This study highlights the synergistic benefits of combining Ginsenoside Rg1 priming with nanoscale engineering and introduces Rg1-ACDVs as a scalable and innovative strategy, offering a promising approach for improving clinical outcomes in MI/RI therapy.