Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent inherited muscle disease. Because in FSHD patients the coexistence of affected and unaffected muscles is common, myoblasts expanded from unaffected FSHD muscles have been proposed as suitable tools for autologous cell transplantation. Mesoangioblasts are a new class of adult stem cells of mesodermal origin, potentially useful for the treatment of primitive myopathies of different etiology. Here, we report the isolation and characterization of mesoangioblasts from FSHD muscle biopsies and describe morphology, proliferation, and differentiation abilities of both mesoangioblasts and myoblasts derived from various affected and unaffected muscles of nine representative FSHD patients. We demonstrate that mesoangioblasts can be efficiently isolated from FSHD muscle biopsies and expanded to an amount of cells necessary to transplant into an adult patient. Proliferating mesoangioblasts from all muscles examined did not differ from controls in terms of morphology, phenotype, proliferation rate, or clonogenicity. However, their differentiation ability into skeletal muscle was variably impaired, and this defect correlated with the overall disease severity and the degree of histopathologic abnormalities of the muscle of origin. A remarkable differentiation defect was observed in mesoangioblasts from all mildly to severely affected FSHD muscles, whereas mesoangioblasts from morphologically normal muscles showed no myogenic differentiation block. Our study could open the way to cell therapy for FSHD patients to limit muscle damage in vivo through the use of autologous mesoangioblasts capable of reaching damaged muscles and engrafting into them, without requiring immune suppression or genetic correction in vitro.
- Facioscapulohumeral muscular dystrophy
- Muscle stem cells
ASJC Scopus subject areas
- Cell Biology