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Inserm. New cells for new purposes: use of gingival fibroblast for arterial repair Antoine LAFONT, MD, PHD, FESC, Hopital Europeen Georges Pompidou INSERM U849 PARIS-DESCARTES University FRANCE. E 00-16. AAA: which target ?. Loss of smooth muscle cells Destruction of elastin network

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E 00-16

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  1. Inserm New cells for new purposes: use of gingival fibroblast for arterial repairAntoine LAFONT, MD, PHD, FESC, Hopital Europeen Georges PompidouINSERM U849 PARIS-DESCARTES University FRANCE E 00-16

  2. AAA: which target ? • Loss of smooth muscle cells • Destruction of elastin network • Increased activity of MMP-9 • Inflammatory reaction

  3. AAA: why cell therapy ? • To restore cells • To restore elastin network • To control MMP-9 activity

  4. AAA: which cell ? • Gingiva: embryo-like repair • A model for arterial repair • No scar/no inflammation • Gingival fibroblast: • Responsible for gingival tissue healing

  5. HYPOTHESIS • Plasticity of HGF considered as embryo like cells • Autologous HGF transferred in aneurysmal wall should modify the pathological remodeling : • enlarging remodeling: aneurysm • Contractil remodeling: stenosis

  6. METHODOLOGY • Cell Culture • Artery Culture • Animal model • 1- Healthy arteries • 2- Stenosis model (Lafont A, 1995) • 3- Aneurism model (Anidjar S, 1992, 1994).

  7. Cell Coculture SMC/HGF3D Coculture Artery/HGF • MMP9 • TIMP1 • Complex MMP9/TIMP1

  8. Human gingival fibroblasts inhibit MMP-9 activity

  9. Decrease of MMP-9 activity is not due to a translation modification

  10. SMC/HGF coculture induce an increase (X7) of MMP-9 inhibitor: TIMP-1.

  11. TIMP-1 translation is also increased:

  12. Increase of MMP-9/TIMP-1 complex induces the inhibition of MMP-9:

  13. Elastic network is protected in presence of human gingival fibroblasts Control Artery + HGF D3 X20 Orcéine D 21

  14. HGF tranfer in healthy arteries: Perls X 20 X 100 HLA detection (1 million de fibroblastes gingivaux injectés) X 40 X 10

  15. Elastic network in elastase model Elastase model Control Orceine X 20

  16. In vivo: Aneurysm model Control Elastase model

  17. HGF injection in aneurysmal arteries: Perls X 5 Perls X 10

  18. Conclusions • MMP-9: a real target to specifically treat AAA • Gingival fibroblast: -able to inhibit MMP-9 expression via TIMP-1 stimulation -easy to collect/amplify • Cell tansplantation: appropriate for AAA

  19. ACKNOWLEDGEMENTS: Bernard Coulomb, CR1 Bruno Gogly, PU-PH Camille Brasselet, PHU, post-doc Eric Durand, PHU , post-doc Sylvie Séguier, MCU-PH Ludovic Couty, ingénieur de recherche Mathilde Lemitre, ITA Dominique Urbain, ITA Karima Ichegour, Agnès Bodineau, AHU, doctorante 2ème année Marco Giacci, DEA Benjamin Fournier, doctorant 2ème année Adrien Naveau, doctorant 3ème année Nicoletta Reynald, doctorante 2ème année

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