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

Motoshi Kozakai, Yuji Narita, Aika Yamawaki-Ogata, Kazuro L. Fujimoto, Masato Mutsuga, Yoshiyuki Tokuda, Akihiko Usui

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)95-104
Number of pages10
JournalExpert Opinion on Biological Therapy
Volume22
Issue number1
DOIs
Publication statusPublished - 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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