Low-intensity pulsed ultrasound as a strategy to boost exosome secretion by adipose-derived stem cells and uptake for myocardial infarction therapy

Acute myocardial infarction (MI) remains a major global health issue, with limited therapeutic strategies to repair damaged myocardial tissue and improve long-term cardiac function. Exosome-based therapies, particularly those derived from adipose-derived stem cells (ADSCs), have shown significant promise in promoting cardiac repair. However, the low yield of exosomes from ADSCs has limited their clinical application. In this study, we investigate the potential of low-intensity pulsed ultrasound (LIPUS) to enhance exosome release from ADSCs and promote myocardial recovery. Our results demonstrate that LIPUS at 0.8 W cm^-2for 10 min effectively increases ADSC-derived exosome production by approximately 50% through inhibiting autophagy. Additionally, LIPUS treatment promotes the uptake of exosomes by hypoxic myocardial cells, further enhancing the therapeutic potential of ADSC-exosomes in MI.<i>In vivo</i>, the combination of LIPUS and exosomes significantly improved cardiac function, reduced inflammation, and attenuated myocardial apoptosis and fibrosis in a rat model of MI. These findings suggest that LIPUS can serve as a non-invasive strategy to boost exosome secretion and uptake, offering a promising approach for MI therapy.