Abstract
BackgroundMesenchymal 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.MethodsBM-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.ResultsAngII 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.ConclusionsMultiple 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.
Highlights
Mesenchymal stem cells (MSCs) are known to be capable of suppressing inflammatory responses
We previously demonstrated that intraabdominal implantation of bone marrow-derived MSCs (BM-MSCs) sheet by laparotomy could attenuate the development of angiotensin II (AngII) induced aortic aneurysm (AA) in apolipoprotein E-deficient mice by anti-inflammation [16]
BM-MSCs inhibited the development of AA in Ang II-infused apoE−/− mice To determine the effects of intravenous administration of BM-MSCs on Ang II-induced AA formation, AngIIinfused apoE−/− mice received multiple intravenous administrations of BM-MSCs or saline via tail vein
Summary
Mesenchymal stem cells (MSCs) are known to be capable of suppressing inflammatory responses. Cell delivery by laparotomy is invasive; we here demonstrated the effects of multiple intravenous administrations of BM-MSCs on AngII-induced AA formation. The pathogenesis of AA is characterized by chronic inflammation in the aortic wall with accumulation of macrophages and degradation of extracellular matrix with increased matrix metalloproteinases (MMPs). Infiltrated inflammatory cells such as macrophages, and lymphocytes cause activation of matrix metalloproteinases, MMP-2 and MMP-9, resulting in the degradation of both collagen and its associated collagenous matrix, along with elastin fragmentation and smooth muscle cell (SMCs) apoptosis, which contribute prominently to AA development [7,8,9]. The positive correlation between inflammatory infiltrates and aneurysmal enlargement [10], as well as regression of established AA by limiting proinflammatory signaling in mice [11], suggest the important role of inflammation in AA pathogenesis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
