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Lentivirus mediated HO-1 gene transfer enhances myogenic precursor cell survival after autologous transplantation in pig

Chauveau, Christine
Anegon, Ignacio
Published in Molecular Therapy. 2008, vol. 16, no. 2, p. 404-10
Abstract Cell therapy for Duchenne muscular dystrophy and other muscle diseases is limited by a massive early cell death following injections. In this study, we explored the potential benefit of heme oxygenase-1 (HO-1) expression in the survival of porcine myogenic precursor cells (MPCs) transplanted in pig skeletal muscle. Increased HO-1 expression was assessed either by transient hyperthermia or by HO-1 lentiviral infection. One day after the thermic shock, we observed a fourfold and a threefold increase in HSP70/72 and HO-1 levels, respectively. This treatment protected 30% of cells from staurosporine-induced apoptosis in vitro. When porcine MPC were heat-shocked prior to grafting, we improved cell survival by threefold at 5 days after autologous transplantation (26.3 +/- 5.5% surviving cells). After HO-1 lentiviral transduction, almost 60% of cells expressed the transgene and kept their myogenic properties to proliferate and fuse in vitro. Apoptosis of HO-1 transduced cells was reduced by 50% in vitro after staurosporine induction. Finally, a fivefold enhancement in cell survival was observed after transplantation of HO-1-group (47.5 +/- 9.1% surviving cells) as compared to the nls-LacZ-group or control group. These results identify HO-1 as a protective gene against early MPC death post-transplantation.
Keywords AnimalsApoptosis/drug effectsBlotting WesternCell Survival/genetics/physiologyCells CulturedFemaleFlow CytometryHSP70 Heat-Shock Proteins/metabolismHeat-Shock Proteins/metabolismHeme Oxygenase-1/metabolismLentivirus/geneticsMyoblasts/cytology/transplantationSkeletal/cytology/drug effects/metabolismRNA Small Interfering/geneticsStaurosporine/pharmacologySwineTransplantation Autologous
PMID: 18026170
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Research groups Culture Primaire de myoblastes humains (208)
Thérapie cellulaire et troubles musculo-squelettiques (960)
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LAUMONIER, Thomas et al. Lentivirus mediated HO-1 gene transfer enhances myogenic precursor cell survival after autologous transplantation in pig. In: Molecular therapy, 2008, vol. 16, n° 2, p. 404-10. doi: 10.1038/sj.mt.6300354 https://archive-ouverte.unige.ch/unige:796

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Deposited on : 2009-02-13

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