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Développement d’une approche de thérapie cellulaire de l’anévrisme de l’aorte abdominale utilisant les fibroblastes gingivaux chez la souris

Abstract : Abdominal aortic aneurysm (AAA), frequently diagnosed in old patients, is characterized by chronic inflammation, vascular cell apoptosis and metalloproteinases-mediated extracellular matrix destruction. Depiste improvement in the understanding of the pathophysiology of the aortic aneurysm disease, no pharmacological treatment is available to limit dilatation and/or rupture. In the study reported here, we tested whether periadventitial allograft of GF prevented abdominal aortic aneurysmal growth and rupture in mice and investigated the mechanisms of vascular protection. In vitro, mouse GF proliferated and produced large amounts of anti-inflammatory cytokines and Timp-1, an inhibitor of metalloproteinases. When layed down in the periadventitial abdominal aorta, we documented that GF survived in vivo, proliferated and organized as a thick layer. Furthermore, GF locally produced Il-10, TGF-β and Timp-1. In an elastase-induced AAA, GF prevented both macrophage and lymphocyte infiltration, elastin degradation and aneurysm growth. Specific invalidation of Timp-1 in GF abolished the beneficial effect of cell therapy. In an Angiotensin II/anti-TGF-β model of AAA, GF cell therapy limited AAA development and prevented abdominal rupture. Gingival fibroblast is a promising cell therapy approach to inhibit aneurysmal progression and rupture through the local production of Timp-1.
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Submitted on : Monday, September 18, 2017 - 12:25:09 PM
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  • HAL Id : tel-01589201, version 1

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Andréas Giraud. Développement d’une approche de thérapie cellulaire de l’anévrisme de l’aorte abdominale utilisant les fibroblastes gingivaux chez la souris. Biologie cellulaire. Université Sorbonne Paris Cité, 2016. Français. ⟨NNT : 2016USPCB029⟩. ⟨tel-01589201⟩

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