title: Bone marrow mesenchymal stem cells stabilize already-formed aortic aneurysms more efficiently than vascular smooth muscle cells in a rat model.
abstract: OBJECTIVE
  Abdominal aortic aneurysms (AAAs) expand because of aortic wall destruction. Enrichment in Vascular Smooth Muscle Cells (VSMCs) stabilizes expanding AAAs in rats. Mesenchymal Stem Cells (MSCs) can differentiate into VSMCs. We have tested the hypothesis that bone marrow-derived MSCs (BM-MSCs) stabilizes AAAs in a rat model.
  
  
  METHODS
  Rat Fischer 344 BM-MSCs were isolated by plastic adhesion and seeded endovascularly in experimental AAAs using xenograft obtained from guinea pig. Culture medium without cells was used as control group. The main criteria was the variation of the aortic diameter at one week and four weeks. We evaluated the impact of cells seeding on inflammatory response by immunohistochemistry combined with RT-PCR on MMP9 and TIMP1 at one week. We evaluated the healing process by immunohistochemistry at 4 weeks.
  
  
  RESULTS
  The endovascular seeding of BM-MSCs decreased AAA diameter expansion more powerfully than VSMCs or culture medium infusion (6.5% ± 9.7, 25.5% ± 17.2 and 53.4% ± 14.4; p = .007, respectively). This result was sustained at 4 weeks. BM-MSCs decreased expression of MMP-9 and infiltration by macrophages (4.7 ± 2.3 vs. 14.6 ± 6.4 mm(2) respectively; p = .015), increased Tissue Inhibitor Metallo Proteinase-1 (TIMP-1), compared to culture medium infusion. BM-MSCs induced formation of a neo-aortic tissue rich in SM-alpha active positive cells (22.2 ± 2.7 vs. 115.6 ± 30.4 cells/surface units, p = .007) surrounded by a dense collagen and elastin network covered by luminal endothelial cells.
  
  
  CONCLUSIONS
  We have shown in this rat model of AAA that BM-MSCs exert a specialized function in arterial regeneration that transcends that of mature mesenchymal cells. Our observation identifies a population of cells easy to isolate and to expand for therapeutic interventions based on catheter-driven cell therapy.
authors.affiliation: CNRS EAC 7054, Centre de Recherches Chirurgicales Dominique Chopin, Faculty of Medicine, Université Paris-Est Créteil, France.
authors.forename: F
authors.initials: F
authors.lastname: Schneider
authors.forename: F
authors.initials: F
authors.lastname: Saucy
authors.forename: R
authors.initials: R
authors.lastname: de Blic
authors.forename: J
authors.initials: J
authors.lastname: Dai
authors.forename: F
authors.initials: F
authors.lastname: Mohand
authors.forename: H
authors.initials: H
authors.lastname: Rouard
authors.forename: J-B
authors.initials: JB
authors.lastname: Ricco
authors.forename: J-P
authors.initials: JP
authors.lastname: Becquemin
authors.forename: M
authors.initials: M
authors.lastname: Gervais
authors.forename: E
authors.initials: E
authors.lastname: Allaire
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D051381:Rats; D011916:Rats, Inbred F344; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat