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(DOC) Efficient

By Chad Ferguson,2014-07-22 02:56
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Efficient

    Efficient

TherapeuticbenefitofTHengineeredmesenchymalstemcellsfor

    ;Parkinson’sdisease.

    ;LuL,ZhaoC,LiuYSunX,DuanC,JiM,ZhaoH,XuQ,YangH

    ;BeijingInstituteforNeuroscience,TheBeijingCenterofNeuralRegenerationandRepairing,CapitalUniversityofMedicalSciences,

    ;Beijing100054,P.R.China.

    ;Thepresentstudywasdesignedtoassessthepotentialofmarrowstromalcells(MSCs)todelivertherapeuticgenes

    ;tothebrainandresultinbiologicallysignificantfunctionalrecovery.Thetyrosinehydroxylase(TH)genewas

    ;transfectedtoMSCswithanadeno.associatedvirusfAAV1vector.MSCsexpressingTHgeneweretransplanted

    ;intothestriatumofParkinson’sdiseasefPD1rat.Theasynvnetricrotationofthesemodelsafterapomorphine

    ;administrationwasdetectedeveryweekaftertransplantatiOn.Sixweeksaftergrafting,alaimalsweresacrificed.

    ;SomebrainsweresectionedtodOTHilammnohistochelnistry.Theotherswereusedtodetectthedoparninelevels

    ;byhighperformanceliquidchromatographandelectrochemicaldetection

(HPLCECD).Theresultsshowedthat

    ;MSCsmultiplyrapidlyandformedfibroblastcolonyformingunitsinprima

    ryculture.Thegeneexpressioneffi

    ;ciencywasabout75%.TheroundsofasymmetricrotationafterapomorphineadlnilfistrationdecreasedafterTH.

    ;engineeredMSCsweregrafted.HistologicalexaminationshowedthatTHgenewasexpressedaroundthetransplan

    ;tationpoints.ThedopaminelevelinthelesionedstriatumofratsinjectedwithTHMSCswassignificantlygreater

    ;thanthatinratstreatedwithLacZMSCsfP<0.05).Allthedatademonstra

    tedthatMSCscouldreadilybegeneti

    ;callyengincered.Therefore,MSCscouldbeusefulgenedeliveryvehiclesofgenetherapyforParkinson’sdisease.

    ;BrainResProtoc.2005,15(1)=4651.(impactfactor:1.816)

    ;Efficienttherapeuticgeneexpressioninculturedrathippocampalneurons ;mediatedbyhumanfoamyvirusvectors:apotentialforthetreatmentof ;neurologicaldiseases.

    ;LiuW,HeX,CaoZ,ShengJ,LiuH,LiZ,LiW

    ;KeyLaboratoryofVirology,MinistryofEducation,CollegeofLifeSciences,WuhanUniversity,Wuhan,People’sRepublicof

    ;China.

    ;Vectorsderivedfromhunaanfoamyvirus(HFV),withtheirnonpathogenicna

tureandawidetissuetropism,have

    ;beensuccessfullyusedasretroviralgenetransfervehicles.However,transductionofprimaryhippocampalneurons

    ;(HNs)withHFVvectorshaslittlebeenstudied.Toinvestigatethepotentialof

    derivedvectoringenetherapy HFV

    ;forneurologicaldiseases,efficientforeigngeneexpressioninculturedratHNswasfirstdemonstratedbysuccessful

    ;enhancedgreenfluorescentprotein(EGFPtransductionthroughaHFVvectorbearingallEGFPexpressioncassette.

    ;Furthcrmore,wetestedtheeffectonHNsthatweretransducedbyanovelHFVvectorexpressingthehuman

    ;?———

    ;46?———

    ;

    ;ghtamicaciddecarboxylase(GAD)eDNA,atherapeuticgeneforneurologicaldisorderssuchasepilepsyand

    ;Parkinson’Sdisease.ThetransducedHNsshowedsignificantincreaseinisoformspecificexpressionofGAD,

    ;synthesisofgammaanainobutyricacid(GABA)andstimulationevoke

    dGABArelease.Thesefindingsindicatedfor

    ;thefirsttimethatculturedratHNscouldbeefficientlytransducedbyHFVvectors,andtheGADexpressingHFV

    ;vectorhaspotentialtherapeuticvalueinthetreatrnentofneurologicaldiseases.Copyright2005S.KargerAG,Basel

    335.(impactfactor:1.776) ;lntervirology.2005,48(5~329

    ;ValproatepretreatmentprotectsdopaminergicneuronsfromLPSinduced

    ;neurotoxicityinratprimarymidbraincultures:roleofmicroglia. ;PengGS,LiG,TzengNS,ChenPS,ChuangDM,HsuYD,YangS,HongJS ;DepartmentofNeurology,TriServiceGeneralHospital,NationalDefense

    MedicalCenter,Taipei,Taiwan,

    ;Parkinson’SdiseaseisaneurOdegeneratiVedisordercharacterizedbyprogressivedegenerationofdopaminergic

    ;(DA)neuronsinthesubstantianigra.Accumulatingevidencesupportsthenotionthatneuroinflalranationisinvolved

    ;inthepathogencsisofthisdisease.Valproate(VPA)haslongbeenusedforthetreatmentofseizuresandbipolar

    ;mooddisorder.InvivoandinvitrostudieshavedemonstratedthatVPAhasneuroDrotectiveandneurotrophic

    ;actions.Inthisstudy,usingprimaryneurongliaculturesfromratmidbrain,

    wedemonstratedthatVPAisapotent

    ;neuroprotectiveagentagainst1ipopolysaccharide(LPS)δΈ€

    inducedneurotoxicity.Resultsshowedthatpretreatment

    ;with0.6naNVPAfor48hrobustlyattenuatedLPSinduceddegenerationof

    dopaminergicneuronsasdeterminedby

    ;[(3)H]dopamineuptakeandcountingofthenumberofTHirneurons.TheneuroprotectiveeffectofVPAwas

    dependentandwasmediated,atleastinpart,throughadecrea;concentration

    seinlevelsofproinflammatoryfactors

    ;releasedfromactivatedmicroglia.Specifically,LPSinducedincreaseinthereleaseofTNFa,NO,andintracelhlar

    ;reactiveoxygenspecieswasmarkedlyreducedinculturespretreatedwithVP

    A.Theseantiinflammatoryeffectsof

    ;VPAweretimeandconcentrationdependentcorrelatedwithadecreaseinthenumberofmicroglia.Thus,our

    ;resultsdemonstratethatprotractedVPApretreatmentprotectsdopaminergic

    neuronsfronlLPS--inducedneurotox--

    ;icitythroughareductioninlevelsofreleasedproinflan-maatoryfactors,andfurthersuggestthattheseantiinflam

    ;matoryeffectsmaybccontributedbyVPAinducedreductionofmicrogliacellnumber.Takentogether,ourstudy

    ;reinforcestheviewthatVPAmayhaveutilityintreatingParkinson’Sdisease.

    ;MolBrainRes.2005,134(1):162169.(impactfactor:1.585) ;--——

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