干细胞治疗自身免疫性疾病.ppt

UB-MSC:thenewgoldstandardtotreatseveralhumandiseases,especiallyautoimmunediseases,InstituteofClinicalMedicine,RenminHospital,HubeiUniversityofMedicine,JunmingTang2015.8,Outline,一、Definition二、Characteristics三、Classification四、Pathogenesis五、Traditionaltherapy六、Biotherapy(antibody、vaccine、genetherapy)七、Celltherapy(DC、HSC、MSC),一、Definition,Autoimmunityrefertotheimmuneresponsestoselfcellsorselfcomponents.Autoimmunediseaserefertothediseasestateresultedfromimmuneresponsesdirectedagainstselfcellsorselfcomponents.,二、Characteristics,Autoimmuneantibodyand(or)autoreactiveTlymphocytecanbedetected.Autoimmuneantibodyand(or)autoreactiveTlymphocytemediateimmuneresponsewhichleadtodamageorfunctionaldisturbanceTheturnoverofpathogeneticconditionrelatewithautoimmuneresponseintensityRecurrentattacksandchronic,三、Classification,Organ-specificautoimmunediseaseGravesdisease、insulin-dependentdiabetesmellitusSystemicautoimmunediseasesystemiclupuserythematosus,四、Pathogenesis,AutoimmuneantibodyDisfunctionimmunologicsystem(autoreactiveTlymphocyte)Geneticsandendocrine,ExamplesofHumanAutoimmuneDiseaseswithPossibleMolecularMimicryasaMechanism,ClinRevAllergyImmunol.2012;42(1):102C11,常见自身免疫病,五、Traditionaltherapy,GeneraltherapyCortisoneImmuneinhibitorsOthers,六、Biotherapy,AntibodyVaccine,PharmaceuticalBiotechnology2012,19(4):364368.ChineseJournalofNewDrugs2011,20(8),Howtobettersolvethesufferingofpatients,Newways,七、GeneandCelltherapy,DC、NK、CIK、B、T、LAKStemcells(HSC、MSC.）,八、StemCelltherapyforAID,1.Definition114:21-27.),2.Celltypes,16,MSC:originandbiologicaltraits,CsarNombela-Arrieta,NatureReviewsMolecularCellBiology12,126-131(2011),Synovium,Cartilage,Dentalpulp,Bonemarrow,Kidney,Pancreas,Adiposetissue,Muscle,Brain,liver,Tonsil,Placenta,UmbilicalCord,Thymus,Pericytes,Amnioticfluid,3.Isolation,culturestoreofmesenchymalstemcellsfromWhartonsjelly,J.BiomedicalScienceandEngineering,2012,5,580-586,Cryobiology.2014Jun;68(3):467-72.,CurrentStemCellResearch20(5):523-44.,Better:autologous/allogenic?,AllogenichealthyBM-MSC,UB-MSC,CellularImmunology293(2015)113121,Summary,.,1.UmbilicalcordderivedMSCsaremoreprimitive,proliferative,regenerative,homingandimmuno-suppressivethantheiradultcounterparts2.HealthyUB-MSCisbetterthanMSCfrompatient-self,6.PreclinicalEfficacyandMechanismsofMesenchymalStemCellsinAnimalModelsofAutoimmuneDiseases,ImmuneNetwork2014;14(2):81-88,7.Mesenchymalstemcellimmunosuppressionofinnate/adaptiveimmunecells,WorldJStemCells2014;6(5):526-539,Differentialtoll-likereceptorstimulationaffectsmesenchymalstemcellimmune-modulation,Summary,Immunosuppression,PermitforapplicationofUB-MSCinhumanAID,CellStemCell17,July2,2015,8.Clinicaltrails:StemcellforAID,Clinicaltrials(registeredasofAug.82015)usingHSC,haematologica|2010;95(2):184-193.,Clinicaltrials(registered)usingMSCDuringHSCtransplantation,MariaEsterBernardo,ImmunologyLetters,Availableonline25June2015,Experimental8(3):940-52.,Summary:FDApermitforUB-MSC,多系统硬化,风湿性关节炎,I型糖尿病,系统性红斑狼疮,狼疮肾炎,肝夏科氏肝硬变,自身免疫性肝炎,IgA肾病,克隆病,色素性视网膜炎,血栓闭塞性脉管炎,进行性面部偏侧萎缩,Take-homemessages,UB-MSC:thenewgoldstandardtotreatseveralhumandiseases,especiallyautoimmuneandneurodegenerativediseases,43,1TangJM,LuoB,XiaoJH,LvYX,LiXL,ZhaoJH,ZhengF,ZhangL,ChenL,YangJY,GuoLY,WangL,YanYW,PanYM,WangJN,LiDS,WanY,ChenSY.VEGF-Apromotescardiacstemcellengraftmentandmyocardialrepairintheinfarctedheart.IntJCardiol.2015;183:221-31.2.XieWB,LiZ,ShiN,GuoX,TangJ,JuW,HanJ,LiuT,BottingerEP,ChaiY,JosePA,ChenSY.Smad2andmyocardin-relatedtranscriptionfactorBcooperativelyregulatevascularsmoothmuscledifferentiationfromneuralcrestcells.CircRes.2013;113(8):e76-86.3.TangJM,WangJN,ZhangL,ZhengF,YangJY,KongX,GuoLY,ChenL,HuangYZ,WanY,ChenSY.VEGF/SDF-1promotescardiacstemcellmobilizationandmyocardialrepairintheinfarctedheart.CardiovascRes.2011;91(3):402-11.4.TangJ,WangJ,YangJ,KongX,ZhengF,GuoL,ZhangL,HuangY.Mesenchymalstemcellsover-expressingSDF-1promoteangiogenesisandimproveheartfunctioninexperimentalmyocardialinfarctioninrats.EurJCardiothoracSurg.2009,36(4):644-50.PMID:19524448.5.TangJ,XieQ,PanG,WangJ,WangM.Mesenchymalstemcellsparticipateinangiogenesisandimproveheartfunctioninratmodelofmyocardialischemiawithreperfusion.EurJCardiothoracSurg.2006;30(2):353-61.6.TangJ,WangJ,ZhengF,YangJ,KongX,GuoL,ZhangL,HuangY.VascularendothelialgrowthfactorpromotescardiacstemcellmigrationviathePI3K/Aktpathway.ExperimentalCellResearch.2009,315(20):3521-3531.7.TangJ,WangJ,KongX,ZhengF,YangJ,GuoL,ZhangL,HuangY.Mesenchymalstemcellsmodifiedwithstromalcell-derivedfactor1improveremodelingviaparacrineactivationofhepatocytegrowthfactorinaratmodelofmyocardialinfarction.MolecularsandCells.2010,29(1):1-10.8.TangJ,WangJ,KongX,YangJ,ZhengF,GuoL,ZhangL,HuangY.Adenovirus-mediatedstromalcell-derived-factor-1alphagenetransferimprovescardiacstructureandfunctionafterexperimentalmyocardialinfarctionthroughangiogenicandantifibroticactions.MolecularBiologyReports.MolBiolRep.2010;37(4):1957-69.9.TangJ,WangJ,ZhengF,KongX,GuoL,YangJ,ZhangL,HuangY.Combinationofchemokineandangiogenicfactorgenesandmesenchymalstemcellscouldenha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