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Titolo:
In vitro and in vivo tetracycline-controlled myogenic conversion of NIH-3T3 cells: Evidence of programmed cell death after muscle cell transplantation
Autore:
Del Bo, R; Torrente, Y; Corti, S; DAngelo, MG; Comi, GP; Fagiolari, G; Salani, S; Cova, A; Pisati, F; Moggio, M; Ausenda, C; Scarlato, G; Bresolin, N;
Indirizzi:
Univ Milan, Dino Ferrari Ctr, Inst Clin Neurol, I-20122 Milan, Italy Univ Milan Milan Italy I-20122 r, Inst Clin Neurol, I-20122 Milan, Italy Osped Maggiore Policlin, IRCCS, I-20122 Milan, Italy Osped Maggiore Policlin Milan Italy I-20122 IRCCS, I-20122 Milan, Italy Assoc La Nostra Famiglia, IRCCS Eugenio Medea, I-23842 Bosisio Parini, Italy Assoc La Nostra Famiglia Bosisio Parini Italy I-23842 isio Parini, Italy
Titolo Testata:
CELL TRANSPLANTATION
fascicolo: 2, volume: 10, anno: 2001,
pagine: 209 - 221
SICI:
0963-6897(200103/04)10:2<209:IVAIVT>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
DUCHENNE MUSCULAR-DYSTROPHY; HIGHER EUKARYOTIC CELLS; MYOBLAST TRANSPLANTATION; DEFICIENT MUSCLE; GENE-EXPRESSION; MYOD FAMILY; APOPTOSIS; DIFFERENTIATION; FIBROBLASTS; THERAPY;
Keywords:
inducible promoter; myogenesis; cell transplantation; muscular dystrophy; apoptosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Bresolin, N Univ Milan, Osped Maggiore Policlin, Inst Clin Neurol, Via Francesco Sforza 35, I-20122 Milan, Italy Univ Milan Via Francesco Sforza 35 Milan Italy I-20122 Italy
Citazione:
R. Del Bo et al., "In vitro and in vivo tetracycline-controlled myogenic conversion of NIH-3T3 cells: Evidence of programmed cell death after muscle cell transplantation", CELL TRANSP, 10(2), 2001, pp. 209-221

Abstract

Ex vivo gene therapy of Duchenne muscular dystrophy based on autologous transplantation of genetically modified myoblasts is limited by their premature senescence. MyoD-converted fibroblasts represent an alternative source of myogenic cells. In this study the forced MyoD-dependent conversion of murine NIH-3T3 fibroblasts into myoblasts under the control of an inducible promoter silent in the presence of tetracycline was evaluated. After tetracycline withdrawal this promoter drives the transcription of MyoD in the engineered fibroblasts, inducing their myogenesis and giving rise to beta -galactosidase-positive cells. MyoD-expressing fibroblasts withdrew from the cellcycle, but were unable to fuse in vitro into multinucleated myotubes. Fivedays following implantation of engineered fibroblasts in muscles of C57BL/10J mice we observed a sevenfold increase of P-galactosidase-positive regenerating myofibers in animals not treated with antibiotic compared with treated animals. After 1 week the number of positive fibers decreased and several apoptotic myonuclei were detected. Three weeks following implantation ofMyoD-converted fibroblasts in recipient mice, no positive "blue" fiber wasobserved. Our results suggest that transactivation by tetracycline of MyoDmay drive an in vivo myogenic conversion of NIH-3T3 fibroblasts and that, in this experimental setting, apoptosis plays a relevant role in limiting the efficacy of engineered fibroblast transplantation. This work opens the question whether apoptotic phenomena also play a general role as limiting factors of cell-mediated gene therapy of inherited muscle disorders.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 19:33:48