title: Intravenous administration of mesenchymal stem cells prevents angiotensin II-induced aortic aneurysm formation in apolipoprotein E-deficient mouse.
abstract: 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.
authors.affiliation: Department of Cardiothoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya Aichi 466-8550, Japan.
authors.forename: Xian-ming
authors.initials: XM
authors.lastname: Fu
authors.forename: Aika
authors.initials: A
authors.lastname: Yamawaki-Ogata
authors.forename: Hideki
authors.initials: H
authors.lastname: Oshima
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ueda
authors.forename: Akihiko
authors.initials: A
authors.lastname: Usui
authors.forename: Yuji
authors.initials: Y
authors.lastname: Narita
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001014:Aortic Aneurysm / Q000378:metabolism / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000235:genetics*; D001854:Bone Marrow Cells / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D004549:Elastin / Q000378:metabolism; D005269:Femur / Q000473:pathology; D007249:Inflammation; D007275:Injections, Intravenous; D008264:Macrophages / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D000804:Angiotensin II; D004549:Elastin; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse