Abstract 364: Vascular Endothelial Growth Receptor 2 (Flk1) Donor Exosomes Drive Angiogenesis

Autor: Skylar Rizzo, Ao Shi, Ryan Mahlberg, Ashley Amontree, Timothy Peterson, Monique Bagwell, D K Arrell, Tyra A Witt, Mary Nagel, Sungjo Park, Michael Sabbah, Mark Li, Parisa Kargaran, Yue Wu, Jialun Li, Yohan Kim, Fabrice Lucien, Steven Moran, Andre Terzic, Atta Behfar
Rok vydání: 2022
Předmět:
Zdroj: Arteriosclerosis, Thrombosis, and Vascular Biology. 42
ISSN: 1524-4636
1079-5642
DOI: 10.1161/atvb.42.suppl_1.364
Popis: Objectives: Peripheral arterial disease is a significant cause of morbidity and mortality. The goal of this study was to develop a novel treatment to promote angiogenesis. Platelets have been previously implicated in angiogenic events; however, platelet activation rather than presence of growth factors has been associated with new blood vessel formation. This study evaluated exosomes purified from activated platelets to determine their potential in promoting angiogenesis both in vitro and in vivo. Methods & Results: Under Current Good Manufacturing Practices, conditioned medium processed from apheresis platelet cultures yielded a purified exosome product (PEP) enriched for CD63, CD9 and Alix. In vitro, PEP drove HUVEC proliferation, migration, and vascular tube formation. Proteomic evaluation showed Flk1 (VEGFR2) was one of the key angiogenic proteins in PEP. HUVECs treated with Flk1 antibody neutralized PEP (anti-Flk1-PEP) showed reduced vascular tube formation compared to PEP. To evaluate in vivo angiogenesis, a rodent model of hindlimb ischemia was treated with sustained release PEP embedded in fibrin glue (PEP/TISSEEL) with blood flow evaluated by SPY angiography at 28 days post-treatment. Animals treated with PEP/TISSEEL showed improved blood flow with significant difference (p Conclusions: Exosome driven donation of Flk1 here promoted angiogenic events and was successfully translated into healing outcomes in the setting of two animal models of peripheral ischemia. This novel insight into biotherapy achievable pro-angiogenesis establishes a clinical-grade off-the-shelf exosome technology for the treatment of peripheral vascular disease.
Databáze: OpenAIRE
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