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成体干细胞再生损伤肌肉 [复制链接]

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发表于 2008-12-31 09:07 |只看该作者 |倒序浏览 |打印
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日期: 2004-05-12 今日/总浏览: 1/559
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3 Z& J( ^. q. F/ B! O) [Skeletalmusclehasaremarkablecapacitytoregeneratefollowingexerciseorinjuryandharborstwodifferenttypesofadultstemcellstoaccomplishthejob:satellitecellsandadultstemcellsthatcanbeisolatedassidepopulation(SP)cells.Acertaingroupofthesestemcellsisinvolvedinmuscletissuerepair,butisonlytriggeredintothemusclecelldevelopmentpathwaybyinjury.Thequestionthenarises:whatmolecularfactorsturntheseadultstemcellsintomusclecells?NowMichaelRudnickiandcolleagueshaveshownthatonegene,Pax7,hasacrucialroleinthisprocess.
0 N! j' R: E9 j5 A6 w$ S7 ^Inpreviousstudies,Rudnicki’sgroupdemonstratedthatPax7isrequiredtoturnadultstemcellsintomusclecellsduringregeneration.Here,theresearchersworkedwithmousemodelsandinvitroexperimentstoinvestigatewhetherPax7issufficienttoinitiatemusclecellformationininjuredtissue.
0 B6 _% J: G. i( A% @) }; PTheyshowthatstemcellstakenfromregeneratingmuscleinmicelackingthePax7genecouldnotbecomemusclecells,andthatbyputtingPax7backintostemcellstakenfromuninjuredmuscle,theycangenerateapopulationofcellsthatreadilydifferentiateintomusclecells.WhenstemcellsengineeredtoexpressPax7proteinswereinjectedintothemusclesofmicelackingdystrophin(theproteindefectiveinmusculardystrophy),thecellsdifferentiated,formingdystrophin-expressingmusclecellsinthedefectivemuscle.Thisshowsthatengineereddonorcellscandifferentiateinlivingtissueandhelprepairdamagedmuscleofrecipientmice.WhentheresearchersinjectedPax7(usingagenetherapyvirus)intothedamagedmuscleofmicelackingPax7,theyobservedtheproductionofmuscle-formingcellsthatnotonlygaverisetodifferentiatedmusclecells,butalsoaidedintissuerepair.& Z6 L! Z; G4 k0 w# Z' v! r
TheresearchersarguethattheseresultsunequivocallyestablishPax7asakeyregulatorofmusclecelldifferentiationinspecificpopulationsofadultstemcellsduringmuscletissueregenerationinmice.IftherapeuticstrategiesthatactivatePax7inadultstemcellscanturnthemintomusclecells,effectivelyreplenishinginjuredordiseasedmuscletissue,there’shopeofreversingthedebilitatingeffectsofprogressivemuscle-wastingdiseases.Thoughtheusefulnessofsuchanapproachinhumanswillrequireintensiveinvestigation,theresultsonthesemouseadultstemcellsareencouraging.
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8 P5 `2 `9 L7 C7 Q9 DCitation:SealeP,IshibashiJ,ScimA,RudnickiMA(2004)Pax7isnecessaryandsufficientforthemyogenicspecificationofCD45 :Sca1 stemcellsfrominjuredmuscle.PLoSBiol2(5):e130DOI:10.1371/journal.pbio.00201309 g* I" {2 P& i- P  q: J" H
        Moreinformation:        http://www.plosbiology.org/plosonline/?request=get-document&doi=10.1371/journal.pbio.0020130
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