Cellular and Molecular Life Sciences

, Volume 68, Issue 4, pp 677–686 | Cite as

Bone marrow-derived mesenchymal cells and MMP13 contribute to experimental choroidal neovascularization

  • Julie Lecomte
  • Krystel Louis
  • Benoit Detry
  • Silvia Blacher
  • Vincent Lambert
  • Sandrine Bekaert
  • Carine Munaut
  • Jenny Paupert
  • Pierre Blaise
  • Jean-Michel Foidart
  • Jean-Marie Rakic
  • Stephen M. Krane
  • Agnès Noel
Research Article

Abstract

In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a neovascularisation into the choroid. RT-PCR analysis revealed that human neovascular membranes issued from patients with AMD expressed high levels of Mmp13. The contribution of MMP13 in choroidal neovascularization (CNV) formation was explored by using a murine model of laser-induced CNV and applying it to wild-type mice (WT) and Mmp13-deficient mice (Mmp13 −/− mice). Angiogenic and inflammatory reactions were explored by immunohistochemistry. The implication of bone marrow (BM)-derived cells was determined by BM engraftment into irradiated mice and by injecting mesenchymal stem cells (MSC) isolated from WT BM. The deficiency of Mmp13 impaired CNV formation which was fully restored by WT BM engraftment and partially rescued by several injections of WT MSC. The present study sheds light on a novel function of MMP13 during BM-dependent choroidal vascularization and provides evidence for a role for MSC in the pathogenesis of CNV.

Keywords

CNV MMP13 Angiogenesis Bone marrow Mesenchymal stem cells 

Abbreviations

AMD

Age-related macular degeneration

BM

Bone marrow

CAM

Choroiallantoic membrane

CNV

Choroidal neovascularization

MSC

Mesenchymal stem cells

RPE

Retinal pigmented epithelium

TIMP

Tissue inhibitor of metalloprotease

Notes

Acknowledgments

The authors acknowledge P. Gavitelli, F. Olivier, M.-R. Pignon, E. Feyereisen, L. Poma, G. Roland and N. Lefin for collaboration and technical assistance. They thank the GIGA imaging and flow cytometry platform for their help. This work was supported by grants from the European Union Framework Program projects (FP7, MICROENVIMET), the Fonds de la Recherche Scientifique Médicale, the Fonds National de la Recherche Scientifique (F.N.R.S., Belgium), the Federation belge contre le Cancer, the Fonds spéciaux de la Recherche (University of Liège), the Centre Anticancéreux près l’Université de Liège, the Fonds Léon Fredericq (University of Liège), the D.G.T.R.E. from the “Région Wallonne” the Interuniversity Attraction Poles Program-Belgian Science Policy (Brussels, Belgium). JL is recipient of a Televie-FNRS grant. SMK was supported by a grant from the US National Institutes of Health.

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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Julie Lecomte
    • 1
  • Krystel Louis
    • 1
  • Benoit Detry
    • 1
  • Silvia Blacher
    • 1
  • Vincent Lambert
    • 1
    • 2
  • Sandrine Bekaert
    • 1
  • Carine Munaut
    • 1
  • Jenny Paupert
    • 1
  • Pierre Blaise
    • 2
  • Jean-Michel Foidart
    • 1
  • Jean-Marie Rakic
    • 2
  • Stephen M. Krane
    • 3
  • Agnès Noel
    • 1
  1. 1.Laboratory of Tumor and Developmental Biology, Tour de Pathologie, CHU (B23), Groupe Interdisciplinaire de Génoprotéomique Appliquée-Research (GIGA-Cancer)University of LiegeLiegeBelgium
  2. 2.Department of OphthalmologyCHULiegeBelgium
  3. 3.Department of Medicine, Center for Immunology and Inflammatory DiseaseHarvard Medical School and Massachusetts General HospitalBostonUSA

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