Tissue Eng Regen Med.  2023 Dec;20(7):1063-1077. 10.1007/s13770-023-00588-z.

Delivery of SAV-siRNA via Exosomes from Adipose-Derived Stem Cells for the Treatment of Myocardial Infarction

• Bai W
• Zhu T
• Zuo J
• Li Y
• Huang X
• Li G

• KMID: 2548528
• DOI: http://doi.org/10.1007/s13770-023-00588-z

Abstract

BACKGROUND
Myocardial infarction (MI) leads to cardiomyocyte death, poor cardiac remodeling, and heart failure, making it a major cause of mortality and morbidity. To restore cardiac pumping function, induction of cardiomyocyte regeneration has become a focus of academic interest. The Hippo pathway is known to regulate cardiomyocyte proliferation and heart size, and its inactivation allows adult cardiomyocytes to re-enter the cell cycle.
METHODS
In this study, we investigated whether exosomes from adipose-derived stem cells (ADSCs) could effectively transfer siRNA for the Hippo pathway regulator Salvador (SAV) into cardiomyocytes to induce cardiomyocyte regeneration in a mouse model of MI.
RESULTS
Our results showed that exosomes loaded with SAV-siRNA effectively transferred siRNA into cardiomyocytes and induced cardiomyocyte re-entry into the cell cycle, while retaining the previously demonstrated therapeutic efficacy of ADSC-derived exosomes to improve post-infarction cardiac function through anti-fibrotic, pro-angiogenic, and other effects.
CONCLUSIONS
Our findings suggest that siRNA delivery via ADSC-derived exosomes may be a promising approach for the treatment of MI.

Keyword

Adipose-derived stem cell; Exosomes; SAV; siRNA; Myocardial infarction