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

Journal of Translational Medicine

Research

Yuji Narita¹  Aika Yamawaki-Ogata¹  Yuichi Ueda¹  Hideki Oshima¹  Xian-ming Fu¹  Akihiko Usui¹ 

[1] Department of Cardiothoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, 466-8550, Nagoya Aichi, Japan;

关键词: Mesenchymal stem cells;    Aortic aneurysm;    Cell transplantation;    Chronic inflammation;    Matrix metalloproteinase;   

DOI  :  10.1186/1479-5876-11-175

 received in 2013-05-12, accepted in 2013-07-17,  发布年份 2013

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Fu et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.