PB1359 - Exosomal miR-3572-5p secreted by photoactivated adipose-derived stem cells contributes to endothelial function

Background: Adipose-derived stem cells (ASCs) therapies are emerging as a promising approach to therapeutic angiogenesis. Therapeutic persistence and reduced primitive stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches. Light activation is promising and the most widely used in various pathologies, especially for promoting tissue regeneration

Aims: The aim of this study is to determine the role of photoactivated ASCs-derived exosomes (Exos) in endothelial cells and angiogenesis.

Methods: We conducted high-throughput miRNA sequencing to detect the miRNA profiles of light-activated ASCs-Exos and used dual-luciferase reporter gene assay, specific miRNA inhibitor, and siRNA to analyze the roles of miRNA and target gene in both in vitro and in vivo contexts.

Results: We show that exosomal miR-3572-5p efficiently enters into the endothelial cells and activates the VEGFR2-AKT pathway by upregulating ELVAL1. Mechanistically, miR-3572-5p binds directly to ELVAL1 mRNA. Transfection of miR-3572-5p inhibitor to non-light-activated ASCs-exosomes increases endothelial cells migration and sprouts. Thus, ASCs-induced exosomal miR-3572-5p promotes endothelial proliferation, migration, and sprouts by ELVAL1 suppression.

Conclusion(s): We reveal an exosomal pathway by which photoactivated ASCs-derived miRNA promotes angiogenesis and proposed future therapeutic strategies of microRNA-based in ischemic diseases.