Alternative therapeutic strategy for existing aortic aneurysms using mesenchymal stem cell-derived exosomes

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-1 beta, TNF-alpha 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.