Exosomes derived from Induced Vascular Progenitor Cells Promote Angiogenesis in vitro and in an in vivo Rat Hindlimb Ischemia Model

Exosomes derived from Induced Vascular Progenitor Cells Promote Angiogenesis in vitro and in an in vivo Rat Hindlimb Ischemia Model

Johnson Takerra K; Zhao Lina; Zhu Dihan; Wang Yang; Xiao Yan; Oguljahan Babayewa; Zhao Xueying; Kirlin Ward G; Yin Liya; Chilian William M; Liu Dong

American Journal of Physiology. Heart and Circulatory Physiology

2019

2019-08

Induced vascular progenitor cells (iVPCs) were created as an ideal cell type for regenerative medicine and have been reported to positively promote collateral blood flow and improve cardiac function in a rat model of myocardial ischemia. Exosomes have emerged as a novel biomedicine that mimics the function of the donor cells. We investigated the angiogenic activity of exosomes from induced vascular progenitor cells (iVPC-Exo) as a cell-free therapeutic approach for ischemia. Exosomes from iVPCs and rat aortic endothelial cells (RAECs) were isolated using a combination of ultrafiltration and size-exclusion chromatography. Nanoparticle tracking analysis revealed that exosome isolates fell within the exosomal diameter (<150 nm). These exosomes contained known markers Alix and TSG101, and their morphology was validated using transmission electron microscopy. Compared to RAECs, iVPCs significantly increased the secretion of exosomes. Cardiac microvascular endothelial cells and aortic ring explants were pretreated with RAEC-Exo or iVPC-Exo, and basal medium was used as a control. iVPC-Exo exerted an in vitro angiogenic effect on the proliferation, tube formation, and migration of endothelial cells and stimulated microvessel sprouting in an ex vivo aortic ring assay. Additionally, iVPC-Exo increased blood perfusion in a hindlimb ischemia model. Proangiogenic proteins (pentraxin-3 and insulin-like growth factor-binding protein-3) and microRNAs (-143-3p, -291b, and -20b-5p) were found to be enriched in iVPC-Exo, which may mediate iVPC-Exo induced vascular growth. Our findings demonstrate that treatment with iVPC-Exo promotes angiogenesis in vitro, ex vivo, and in vivo. Collectively, these findings indicate a novel cell-free approach for therapeutic angiogenesis.

angiogenesis; endothelial cell; exosome; microRNA; progenitor cell

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