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2013-05-23 - Colloque/Présentation - poster - Anglais - 1 page(s)

Lancelot Céline , Carnac G, Nonclercq Denis , Delrée Paul, Coppée Frédérique , Belayew Alexandra , "Development of fibrosis and its impact on muscle regeneration in FSHD muscle" in Journée de l'institut santé, Mons, Belgique, 2013

  • Codes CREF : Pathologies particulières (DI3370)
  • Unités de recherche UMONS : Biologie moléculaire (M122)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)
  • Centres UMONS : Mind & Health (CREMH)

Abstract(s) :

(Anglais) Development of fibrosis and its impact on muscle regeneration in FSHD muscle Céline Lancelot, Gilles Carnac, Denis Nonclercq, Paul Delrée, Dalila Laoudj-Chenivesse, Alexandra Belayew, Frédérique Coppée 1 Laboratory of Molecular Biology, UMONS, Mons, Belgium; 2 Laboratory of Physiology and experimental medicine, INSERM U1046, Montpellier, France; 3 Laboratory of Histology, UMONS, Mons, Belgium; 4 Pathology and Genetic Institute , IPG, Gosselies, Belgium. Facioscapulohumeral dystrophy (FSHD) is an inherited disorder characterized by atrophy and muscle weakness progressing in an asymmetric antero-posterior gradient. This inherited disorder affects 1/17000 individuals at birth. Our histological analysis of affected FSHD muscles showed an extensive fibrosis and a proliferation of adipose tissue gradually replacing muscle fibers. These areas coexist with muscle fibers without major histological alterations. Despite the significant muscle damage, low muscle regeneration has been demonstrated in this disease compared to other muscular dystrophies. The extracellular matrix (ECM) is a major component of the satellite cell (SC) niche. Other muscle progenitor cells can also be recruited into this niche after muscle damage. Indeed, after muscle injury, quiescent SC (or mesenchymal cells recruited into the muscle) are activated and divide to provide myoblasts that repair the damaged muscle fibers. However changes in the ECM composition can alter muscle regeneration. We hypothesized that modifications in the ECM composition of FSHD muscles are contributing to the observed low muscle regeneration. Our preliminary results confirm an early thickening of ECM unfavorable to muscle regeneration in areas without histological abnormalities of affected FSHD muscles. The fibroblasts produce most components of the ECM. Thus alterations of resident fibroblasts in FSHD muscles could contribute to the inefficiency of muscle regeneration in this disease. Indeed, our preliminary data suggest in vitro and in vivo deregulations of some CM components. In order to characterize the fibrosis in FSHD muscles we established fibroblast primary cultures from control and FSHD muscle biopsies. We isolated fibroblasts from muscle biopsy-derived cells by magnetic sorting with 50-nm superparamagnetic particles that are conjugated to highly specific antibody against a particular antigen on the fibroblast surface. The cell suspension labeled with magnetic particles is applied to a column which contains a matrix composed of ferromagnetic spheres. When placed on a magnetic separator, the spheres amplify the magnetic field by 10,000-fold, thus inducing a high gradient within the column. The space between the spheres is several times larger than cultured cells. This allows the cells to freely flow through the column. The magnetically labeled cells are retained within the column while unlabeled cells flow through. After a washing step, the column is removed from the magnetic field of the separator, and the target cells are eluted from the column. The identity of our cultures was confirmed using different cell markers (vimentin, collagen I and CD 90). This material will allow us to determine whether fibrosis is an early event in FSHD and could contribute to the incorrect response of progenitor muscle cells. We will also investigate the role of the ECM in muscle regeneration and the genes deregulated in FSHD involved in this process. We believe, this analysis will be essential before any clinical trial to restore the function of SC or other muscle progenitor cells.


Mots-clés :
  • (Anglais) FSHD