Pendant le Congrès Myologie 2005, le Dr COSSU a présenté le jeudi 12 mai 2005, lors du symposium parallèle "Transplantation de cellules souches dans les maladies neuromusculaires" une communication dont le titre est : Mésingioblastes, cellules souches d'origine vasculaire et réparation musculaire chez des modèles animaux de dystrophie musculaire.

 

 

 

MESOANGIOBLASTS, VESSEL ASSOCIATED STEM CELLS, REPAIR SKELETAL MUSCLE IN
ANIMAL MODELS OF MUSCULAR DYSTROPHIES.

In the last years several types of mesoderm stem cells have been identified and tentatively characterized in the bone marrow and other tissues of the adult, as well as in the developing vessels of the fetus. Most if not all these progenitors appear to be associated with the micro-vascular niche. It is currently unknown how many different mesoderm progenitor/stem cells (mesenchymal stem cells/ multipotent adult progenitors/ mesoangioblasts) exist in mammals. Similarly unknown are their reciprocal lineage relationships.
In 1998 we reported that the bone marrow contains progenitors able to differentiate into skeletal muscle following bone marrow transplantation (BMT) into lethally-irradiated recipient mice. Searching for the origin of these progenitors, we identified cells that are physically associated with the embryonic dorsal aorta in avian and mammalian embryo and can grow extensively in vitro. We termed these cells “mesoangioblasts”. When transplanted in vivo, mesoangioblasts give rise to multiple differentiated mesodermal phenotypes such as smooth and skeletal muscle, cartilage and bone. Their ability to extensively self-renew in vitro, while retaining multipotency, qualifies mesoangioblasts as a novel class of stem cells. Mesoangioblasts express initially a number of early endothelial markers (Flk-1, Tie-2, CD34 and Kit) but with time in culture they loose expression of many endothelial markers while acquiring markers of perycytes such as Sca-1 and Smooth alpha actin. This suggests that culture conditions select the growth of a cell type probably representing an angioblast in the process of producing a perithelial cell. Thus mesoangioblasts not only emerge as an unexpected source of progenitors for skeletal muscle and a variety of other mesoderm-derived tissues, but also reveal a lineage relationship between progenitors of vascular and extra-vascular mesodermal tissues, with important basic and applied implications. When both wild type or dystrophic, genetically corrected, mesoangioblasts were delivered intra-arterially to dystrophic muscle of a-sarcoglycan KO mice (a model for limb girdle muscular dystrophy), they resulted in a dramatic functional amelioration of the dystrophic phenotype. This was due to the widespread distribution of donor cells through the capillary network and to an intrinsic defect of proliferation in the resident satellite cells, a situation that created a selective advantage for donor cells.  Experiments on the GRMD dystrophic dogs are in progress and results will be described.