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

• Published in: Journal of translational medicine 2013-07, Vol.11 (1), p.175-175, Article 175
• Main Authors: Fu, Xian-ming, Yamawaki-Ogata, Aika, Oshima, Hideki, Ueda, Yuichi, Usui, Akihiko, Narita, Yuji
• Format: Article
• Language: English
• Subjects: Adipocytes; Angiotensin; Angiotensin II - metabolism; Animals; Aorta - metabolism; Aortic Aneurysm - metabolism; Aortic Aneurysm - prevention & control; Aortic aneurysms; Apolipoproteins; Apolipoproteins E - genetics; Bone Marrow Cells - cytology; Care and treatment; Clinical trials; Cytokines - metabolism; Development and progression; Disease Progression; Drug dosages; Elastin - metabolism; Experiments; Femur - pathology; Genetic aspects; Inflammation; Injections, Intravenous; Laboratory animals; Macrophages; Macrophages - metabolism; Male; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medical research; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - cytology; Mice; Mice, Inbred C57BL; Mice, Knockout; Pathogenesis; Physiological aspects; Rodents; Stem cells; Surgery; Transplantation
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/1479-5876-11-175

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. 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. 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. 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.