Journal of Cell Science o:10.1242/jcs.115220 doi: 6147–6156 125, Science Cell of Journal 2012 October 18 Accepted scuilfrhmnseea ucepeusrcell precursor muscle skeletal survival gene, human target for retinoid crucial new is a 3, peroxidase Glutathione Article Research ta. 00.Atog uhposria taeiswr on to of found were inhibition strategies pro-survival such (Drowley the Although cells 2010). stem al., impairs Conversely, muscle-derived et activity of capacity 2004). glutathione al., regenerative decreasing et the al., by Rodriguez-Porcel capacity et improves 2010; antioxidant of al., molecules Suzuki et pre-treatment antioxidant 2010; (Drowley with The survival cells graft experiments. precursor transplantation muscle cell in rapid damage cause from death might suggested transplanted derived implantation, have intramuscular presumably data from is of resulting Recent which 1993). Partridge stress, rates al., 1995; oxidative et al., that Tremblay et survival 1989; Mendell al., 1997; also poor et al., was et trials to (Gussoni clinical myoblasts initial attributed in transfer as partially important, myoblast muscle are such of tissue and host failure limitations into the Although spread necrosis limited 1997). or fiber rejection al., immune and by et myopathies characterized (Gussoni inherited a weakness are of represents treatment that transplantation the diseases myoblast for tubes approach 1989), my viable hybrid al., form to et fibers (Partridge muscle endogenous cells) with precursor fuse muscle can (skeletal myoblasts transplanted Because Introduction of Knockdown myoblasts. words: Key human in gene target acid retinoic potential derived ( a myoblasts 3 as dystrophic peroxidase human in glutathione enzyme, adherent maintained revealed expression were damage peroxide, antioxidant aldehyde gene acid cytotoxic hydrogen antioxidant retinoic an the high by of of reduced encoding analysis effects acid induced that aldehyde RT-qPCR The retinoic stress activity, patients. assays. with demonstrated facioscapulohumeral oxidative transplantation Pre-treatment is detoxifying from we in acid adhesion. to its retinoic survival for exposed Recently, whether myoblast capacity to examined when enhanced their cells. we addition and lost that therefore, and stem In acid; showed apoptosis retinoic myoblasts. We muscle entered to improve myoblasts A viability. human of vitamin to myoblast of of viability and for oxidation viability irreversible regeneration important the the increased characterize muscle catalyze and control with also identify skeletal can to that associated adult dehydrogenase important is genes therefore efficient is activity ensure target It diseases. to dehydrogenase their muscle crucial skeletal and degenerative is in damages molecules transplantation cell cytotoxic of from efficacy cells therapeutic satellite of Protection Summary work this to equally ` contributed authors *These 4 3 2 1 Haddad El Marina P3lvl a aeipratipiain o h iblt fhmnmsl tmcells. stem muscle human of and viability status in the retinoid impaired Therefore, for were acid. implications acid retinoic retinoic important of of effects have effects antioxidative may anti-cytotoxic the The levels regulates death. GPx3 GPx3 cell that and indicates species which oxygen myoblasts, reactive GPx3-inactivated in elevation induced RNA interfering mlePasserieux Emilie uhrfrcrepnec ( correspondence for Author eateto ilg,Fclyo cecsI,Lbns nvriy die lMt,Lebanon Matn, el Jdeidet University, Lebanese De II, Montpellier, Sciences de of CHRU Faculty Biology, of Department Universite UMR866, INRA, Universite U1046, Inserm 02 ulse yTeCmayo ilgssLtd Biologists of Company The by Published 2012. P3 iai ,Rtni cd ybat,Fcocplhmrldsrpy(SD,Transplantation (FSHD), dystrophy Facioscapulohumeral Myoblasts, acid, Retinoic A, Vitamin GPx3, [email protected] 1, 1 ln Hamade Aline , otele ,Universite 1, Montpellier ´ preetd hsooi lnqe 49 otele ee ,France 5, cedex Montpellier 34295 Clinique, Physiologie de ´partement ,EieJean Elise *, otele ,Universite 1, Montpellier ´ 1, ) ,AmdTurki Ahmed *, 3 aqe Mercier Jacques , otele ,325Mnplir France Montpellier, 34295 2, Montpellier ´ otele ,300Mnplir France Montpellier, 34060 2, Montpellier ´ 1 ,Ge rl Hugon ´rald 1,4 aiaLaoudj-Chenivesse Dalila , h nacmn fcl uvvlsol eapicplga fcell of goal principal a techniques. be is Therefore, limit should transplantation survival further transplantation. 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(GE France). antibody and 1/1000; anti-goat PBS or diluted anti-mouse in conjugated (Sigma-Aldrich; 1/ washed anti-cyclinA diluted were v/v); monoclonal Membranes France; 1/500; and Souffelweyersheim, diluted v/v); (Euromedex, Biotechnology; 1000; beta Cruz (Santa anti-RXR beta monoclonal 1/500, diluted anti-RAR Germany; polyclonal Heildelberg, v/v); Biotechnology, Cruz (Santa alpha anti-RAR n ieFH ains e al ) o ybattaslnain i iewere mice six transplantation, myoblast Mann– For 1). using Table injected. see determined patients; FSHD five was and differences means the are of with tests, significance Whitney statistical The analysis Statistical mg/kg by 10 weeks and 5 hydrochloride at ketamin (1 anesthetized myoblasts mg/kg FSHD 100 were Human of France) xylasin. cedex, injection the L’arbresle intraperitoneal by France). River, Anti-Cance approved Centre Montpellier, were (Charles the and of Lamarque, Committee animals Use d’Aurelle-Paul on and Care performed Animal were Institutional procedures surgical All transplantation Cell elne,F . aa,A . evs .A n er,M J. M. Berry, and A. M. Reeves, V., A. Raman, P., F. Bellinger, Laoudj- A. and T. Partridge, and Y. N. C. Vassetzky, Pagel, E., J. J., Morgan, R., Mercier, J. Beauchamp, S., Flavier, G., Carnac, M., A. D. Barro, Lowe, and L. G. Warren, M., S. Greising, A., K. Baltgalvis, E. A. Balber, A. Palou, and L. M. Bonet, J., Ribot, J., Amengual, Cre S., Vincent, M., Vandromme, G., Carnac, O., Albagli-Curiel, References at http://jcs.biologists.org/lookup/suppl/doi:10.1242/jcs.115220/-/DC1 online available material Supplementary M.E.H.]. of [to 1 Universitaire Montpellier Regional of Hospitalier University PhD a and Centre and Montpellier the G.C.]; Franc to from Association 14903 number studentship the 2010, by MNM2 [grant supported Myopathies was work continuously This who Funding FSH’ AMIS ‘Association study. the this the to supported grateful are from We suggestions. her patients for Hokayem Marie thank We Acknowledgements eemnn h ecnaeo ua el qatfe yFC)adtetotal the and FACS) by (quantified by cells quadriceps cells. the human We into of of injected FACS. number were percentage were by that cells the analyzed cells The human and determining of recover. Dickinson) number to actual to (Becton cells the hours CD56 mouse derived 24 host anti-human for and with plated cells days labeled and human 2 isolated implanted or the were injection allow cells after Immediately muscle-derived muscle. implantation, quadriceps after the into implanted were att,P,Lsue . ucee,P n laad V. Allamand, and P. Guicheney, A., Lescure, P., Castets, A. Bonnieu, and A. Levin, O., Albagli-Curiel, G., Carnac, hn,W . ed,S . i .P,Ynd,K,Hre,R n u R. Wu, and R. Harper, K., Yoneda, P., Y. Di, P., S. Reddy, H., W. Chang, xii opooia ifrnito defects. differentiation morphological exhibit D. Chenivesse, 2171-2176. disease. human in selenoproteins of function cell-like source. stem myogenic with precursors the of as minority properties discrete a reveal transplantation myoblast of skeletal mouse in expression gene antioxidant and and muscle. receptors activities, estrogen characteristics, regulates tissues: normal medicine. regenerative from in uses populations emerging cell progenitor cells. mice. muscle of muscle murine skeletal in 16 C2 capacity oxidation in lipid increases triiodothyronine and acid retinoic Differentiation by relieved A. Bonnieu, kltlmsl:fo iesst function. to diseases from muscle: skeletal Myf5. gene determination muscle the of expression the regulates euaino hoeoi eeepeso yvtmnAi ua iwyepithelial airway human in A vitamin by expression cells. gene thioredoxin of Regulation 585-591. , P3mdae Aatoiatefcs6155 effects antioxidant RA mediates GPx3 m .Rsi.Cl o.Biol. Mol. Cell Respir. J. Am. LSONE PLoS 6 ...( s.e.m. 21) ocs eiw leyedhdoeaebih tmand stem bright dehydrogenase aldehyde review: Concise (2011). 19) eu-nue niiino ygnssi differentially is myogenesis of inhibition Serum-induced (1993). 52 21) ybat rmafce n o-fetdFH muscles FSHD non-affected and affected from Myoblasts (2010). 201-210. , P n 5 5 vle f00 and 0.05 of -values e10164. , ifrn utrsdrvdfo iehatyhmnadults human healthy five from derived cultures different 3 .Cl Biol. Cell J. 6 26 10 627-635. , tmCells Stem 5 P ,ete nrae rtetdwt RA, with treated or untreated either ), .Ml e.(Berl.) Med. Mol. J. # ice.J. Biochem. .1rgre ssgiiat Values significant. as regarded 0.01 .Cl.Ml Med. Mol. Cell. 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