MyoD expression restores defective myogenic differentiation of human mesoangioblasts from inclusion-body myositis muscle.
Inflammatory myopathies (IM) are acquired diseases of skeletal muscle comprising dermatomyositis (DM), polymyositis (PM), and inclusion-body myositis (IBM). Immunosuppressive therapies, usually beneficial for DM and PM, are poorly effective in IBM. We report the isolation and characterization of mesoangioblasts, vessel-associated stem cells, from diagnostic muscle biopsies of IM. The number of cells isolated, proliferation rate and lifespan, markers expression, and ability to differentiate into smooth muscle do not differ among normal and IM mesoangioblasts. At variance with normal, DM and PM mesoangioblasts, cells isolated from IBM, fail to differentiate into skeletal myotubes. These data correlate with lack in connective tissue of IBM muscle of alkaline phosphatase (ALP)-positive cells, conversely dramatically increased in PM and DM. A myogenic inhibitory basic helix-loop-helix factor B3 is highly expressed in IBM mesoangioblasts. Indeed, silencing this gene or overexpressing MyoD rescues the myogenic defect of IBM mesoangioblasts, opening novel cell-based therapeutic strategies for this crippling disorder.
Morosetti
Roberta
R
Department of Neurosciences and Interdisciplinary Laboratory for Stem Cell Research and Cellular Therapy, Catholic University, Largo A. Gemelli 8, 00168 Rome, Italy.
Mirabella
Massimiliano
M
Gliubizzi
Carla
C
Broccolini
Aldobrando
A
De Angelis
Luciana
L
Tagliafico
Enrico
E
Sampaolesi
Maurilio
M
Gidaro
Teresa
T
Papacci
Manuela
M
Roncaglia
Enrica
E
Rutella
Sergio
S
Ferrari
Stefano
S
Tonali
Pietro Attilio
PA
Ricci
Enzo
E
Cossu
Giulio
G
D000469:Alkaline Phosphatase / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D034741:RNA, Small Interfering / Q000235:genetics
D000469:Alkaline Phosphatase; D051792:Basic Helix-Loop-Helix Proteins; D017570:MyoD Protein; D034741:RNA, Small Interfering; C422085:BHLHE41 protein, human; C057363:MyoD1 myogenic differentiation protein