Abstract

Introduction: Recently, exosomes secreted by menstrual mesenchymal stem cells (MenSC) have been identified as inhibitory agents of tumor angiogenesis in prostate and breast cancer. However, their direct effect on endothelial cells and paracrine mediators, as well as their mechanism of action, have not yet been investigated. Material and Methods: MenSC-exosomes purity and integrity were characterized according to the ISEV guidelines. HUVEC and HMEC-1 endothelial cells were used to determine the anti-angiogenic effect of exosomes treatment through different in-vitro tests such as cytotoxicity, apoptosis, VEGF secretion and tube-formation assays. Hamster buccal pouch carcinoma as a preclinical model for human oral squamous cell carcinoma was used to demonstrate the anti-angiogenic effect of intra-tumoral injections of exosomes. HTG EdgeSeq miRNA whole transcriptome assay (NGS) were carried out to analyze the miRNA profile of exosomes from 4 independent donors samples. Results: MenSC-exosomes were efficiently taken up by endothelial cells. Exosome-treatment increased cytotoxicity and apoptosis, and reduced VEGF secretion and tube-formation of endothelial cells in a dose dependent manner. MenSC-exosomes injections induced a significant antitumor effect associated with a loss of tumor vasculature in-vivo. The data from the miRNA profile revealed that the 100% of the top 25 common miRNAs enriched in MenSCs-exosomes regulate tumor growth by targeting key multiple oncogenic signaling pathways. Discussion: These results address menstrual stem cell exosomes as potential anti-angiogenic agents for neoplastic conditions treatment. Acknowledgements: FONDECYT REGULAR #1190411, C4C&Regenero.