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Empagliflozin-pretreated mesenchymal stem cell-derived extracellular vesicles facilitate cardiac repair via AGGF1

Qianwen Chen, Qing-Xiang Gu, Jun Wei, Li Deng, Ye Deng, Jingyi Wang, Jianya Huang, T. Sun et al.

Journal of Nanobiotechnology, 2026

Abstract

BACKGROUND

Current treatment modalities can only reap a limited efficacy in reversing myocardial damage and promoting functional recovery in patients with myocardial infarction. Therefore, there is an urgent need to explore new therapeutic approaches to enhance cardiac repair.

METHODS

MSCs were pretreated with empagliflozin to obtain EMPA-EVs, with non-pretreated MSC-EVs serving as controls. In vitro experiments were conducted to evaluate the effects of the two types of EVs on macrophage phenotypic transformation, cardiomyocyte apoptosis, and vascular endothelial cell lumen formation. In vivo experiments, a rat model of myocardial infarction was constructed, and EMPA-EVs, non-pretreated MSC-EVs, or phosphate-buffered saline were administered via myocardial injection. Post-treatment assessments included left ventricular ejection fraction, myocardial infarction area, and levels of pro-inflammatory cytokines in myocardial tissue. In addition, AGGF1 was depleted in EMPA-EVs to observe their anti-apoptotic, anti-inflammatory, and pro-angiogenic effects.

RESULTS

Compared with non-pretreated MSC-EVs, EMPA-EVs increased the proportion of macrophages transforming into anti-inflammatory phenotypes, decreased the rate of apoptotic cardiomyocytes, and promoted the formation of vascular endothelial cell lumen. Animal experiments showed that the left ventricular ejection fraction of rats in the EMPA-EVs group was higher than that in the control group, the myocardial infarction area was…

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