Alternative therapeutic strategy for existing aortic aneurysms using mesenchymal stem cell–derived exosomes. (2nd January 2022)

• Record Type: Journal Article
• Authors: Kozakai, Motoshi; Narita, Yuji; Yamawaki-Ogata, Aika; Fujimoto, Kazuro L; Mutsuga, Masato; Tokuda, Yoshiyuki; Usui, Akihiko
• Is Part Of: Expert opinion on biological therapy. Volume 22:Number 1(2022)
• Page Start: 95
• Page End: 104
• Publication Date: 2022-01-02
• Subjects: Aortic aneurysm -- exosome -- extracellular vesicles -- mesenchymal stem cells -- microRNA -- stem cell therapy; Gene therapy -- Periodicals; Protein drugs -- Periodicals; Peptide drugs -- Periodicals; Immunotherapy -- Periodicals; Drug delivery systems -- Periodicals; 615.5
• DOI: 10.1080/14712598.2022.2005575
• Languages: English
• ISSNs: 1471-2598

Abstract

ABSTRACT: Background: Several studies demonstrated the therapeutic potential of mesenchymal stem cell–derived exosomes (MSC-exs) based on their anti-inflammatory properties. The objective was to determine the therapeutic effects of MSC-exs on aortic aneurysms (AAs) caused by atherosclerosis. Research design and methods: Apolipoprotein E knockout mice with AAs induced by angiotensin II were injected with MSC-exs or saline as a control. The change in the diameter of the aorta was measured. The expression of AA-related proteins and the histology of the aortic wall were investigated at 1 week after treatment. MicroRNA and protein profiles of MSC-exs were examined. Results: MSC-exs significantly attenuated AA progression (2.04 ± 0.20 mm in the saline group and 1.34 ± 0.13 mm in the MSC-ex group, P = 0.004). In the MSC-ex group, the expression of IL-1β, TNF-α and MCP-1 decreased, and expression of IGF-1 and TIMP-2 increased. MSC-ex induced the M2 phenotype in macrophages and suppressed the destruction of the elastic lamellae in the aortic wall. MSC-exs contained high levels of 10 microRNAs that inhibit AA formation and 13 proteins that inhibit inflammation and promote extracellular matrix synthesis. Conclusions: MSC-ex might be a novel alternative therapeutic tool for treatment of existing AAs.