Intravenous administration of mesenchymal stem cells prevents angiotensin II-induced aortic aneurysm formation in apolipoprotein E-deficient mouse

BACKGROUND: Mesenchymal stem cells (MSCs) are known to be capable of suppressing inflammatory responses. We previously reported that intra-abdominal implantation of bone marrow-derived MSCs (BM-MSCs) sheet by laparotomy attenuated angiotensin II (AngII)-induced aortic aneurysm (AA) growth in apolipoprotein E-deficient (apoE(−/−)) mice through anti-inflammation effects. However, cell delivery by laparotomy is invasive; we here demonstrated the effects of multiple intravenous administrations of BM-MSCs on AngII-induced AA formation. METHODS: BM-MSCs were isolated from femurs and tibiae of male apoE(−/−) mice. Experimental AA was induced by AngII infusion for 28 days in apoE(−/−) mice. Mice received weekly intravenous administration of BM-MSCs (n=12) or saline (n=10). After 4 weeks, AA formation incidence, aortic diameter, macrophage accumulation, matrix metalloproteinase (MMP)’ activity, elastin content, and cytokines were evaluated. RESULTS: AngII induced AA formation in 100% of the mice in the saline group and 50% in the BM-MSCs treatment group (P < 0.05). A significant decrease of aortic diameter was observed in the BM-MSCs treatment group at ascending and infrarenal levels, which was associated with decreased macrophage infiltration and suppressed activities of MMP-2 and MMP-9 in aortic tissues, as well as a preservation of elastin content of aortic tissues. In addition, interleukin (IL)-1β, IL-6, and monocyte chemotactic protein-1 significantly decreased while insulin-like growth factor-1 and tissue inhibitor of metalloproteinases-2 increased in the aortic tissues of BM-MSCs treatment group. CONCLUSIONS: Multiple intravenous administrations of BM-MSCs attenuated the development of AngII-induced AA in apoE(−/−) mice and may become a promising alternative therapeutic strategy for AA progression.