TY - JOUR
T1 - MyoD expression restores defective myogenic differentiation of human
mesoangioblasts from inclusion-body myositis muscle.
AU - Mirabella, Massimiliano
AU - Broccolini, Aldobrando
AU - Ricci, Enzo
AU - Morosetti, Roberta
AU - Gliubizzi, Carla
AU - Gidaro, Teresa
AU - Papacci, Manuela
AU - Rutella, Sergio
AU - Tonali, Pietro Attilio
AU - De Angelis, Luciana
AU - Tagliafico, Enrico
AU - Sampaolesi, Maurilio
AU - Roncaglia, Enrica
AU - Ferrari, Stefano
AU - Cossu, Giulio
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - IBM
KW - mesoangioblasts
KW - muscle diseases
KW - stem cells
KW - IBM
KW - mesoangioblasts
KW - muscle diseases
KW - stem cells
UR - http://hdl.handle.net/10807/8924
M3 - Article
VL - 2006
SP - 16995
EP - 17000
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
ER -