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

Journal of Translational Medicine

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

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

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

Others  :  827074
DOI  :  10.1186/1479-5876-11-175

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

【 摘 要 】

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.

【 授权许可】

   
2013 Fu et al.; licensee BioMed Central Ltd.

【 图 表 】

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