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

Tissue Eng Regen Med. 2023 Dec;20(7):1063-1077. doi: 10.1007/s13770-023-00588-z. Epub 2023 Oct 6.

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.

Keywords: Adipose-derived stem cell; Exosomes; Myocardial infarction; SAV; siRNA.

MeSH terms

  • Animals
  • Exosomes* / metabolism
  • Mice
  • Myocardial Infarction* / genetics
  • Myocardial Infarction* / therapy
  • Myocytes, Cardiac
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA, Small Interfering / pharmacology
  • Stem Cells

Substances

  • RNA, Small Interfering