干细胞治疗1型糖尿病_问题与前景

191920150507ChineseJournalofTissueEngineeringResearchMay7,2015Vol.19,No.19P.O.Box10002,Shenyang110180:A:2095-4344(2015)19-03096-062015-04-02:2015-04-021(110004)11β213β11β,11β1type1diabetesmellitusstemcellstemcelltherapyregenerationtreatmentstem-celdifferentiationstem-celltransplantationimmunesuppressioninsulinsecretingcellsisletβ-cellstherapeuticeffect20032015PubMed1421ββ1.1[J].201519(19):3096-3101.doi:10.3969/j.issn.2095-4344.2015.19.024Stemcelltherapyfortype1diabetesmellitusBaiYu(FirstDepartmentofEndocrinology,ShengjingHospital,ChinaMedicalUniversity,Shenyang110004LiaoningProvince,China)AbstractBACKGROUND:Type1diabetesmellitusisanautoimmuneattackcharacterizedbytheselectivedestructionofpancreaticcells.Patientsneedtorelyonexternalinsulintosurvive,andthereisalackofspecifictreatment.OBJECTIVE:Toreviewthesourceofallkindsofstemcells,differentiationcapacity,self-exclusionandexistingproblems,andtoprovidethebasisforregenerationtreatmentoftype1diabetesmellitus.METHODS:Inordertosearchrelevantarticleaboutstemcelltherapiesfortype1diabetesmellitusfromPubMeddatabase(from2003to2015),acomputer-basedsearchwasperformedusingthekeywordsof“type1diabetesmellitus,stemcell,stemcelltherapy,regenerationtreatment,stem-celldifferentiation,stem-celltransplantation,immunesuppression,insulinsecretingcells,isletβ-cells,therapeuticeffect”inEnglish.Finally,42articleswerechosenforfurtheranalysis.RESULTSANDCONCLUSION:Stemcelltherapyfortype1diabetesmellitushasattractedquitealotofattentions.Restorationofdamagedβ-cellsbyexogenousstemcelltransplantationisthecurrentlyidealtherapeuticoptions,thatis,stemcellsculturedundersuitableconditionscanbeinducedintoisletβ-cellsthathaveendocrinefunction.Throughallkindsofresearch,thispaperexpoundsthesourceofstemcells,directionaldifferentiation,purification,immunesuppressioncharacteristicsandexistingproblems,anditalsohasadiscussionfortheoccurrenceanddevelopmentoftype1diabetesmellitussoastoselectthebestschemeofstemcells,whichhelpstocurethedisease.Subjectheadings:DiabetesMellitus,Type1;Insulin-SecretingCells;StemCellTransplantationBaiY.Stemcelltherapyfortype1diabetesmellitus.ZhongguoZuzhiGongchengYanjiu.2015;19(19):3096-3101..1ISSN2095-4344CN21-1581/RCODEN:ZLKHAH3097(IDF)780001513%150.1/100000[1]1βββ11Dataandmethods1.120032015PUBMED1type1diabetesmellitusstemcellstemcelltherapyregenerationtreatmentstem-celldifferentiationstem-celltransplantationimmunesuppressioninsulinsecretingcellsisletβ-cellstherapeuticeffect1.21.3type1diabetesmellitus,stemcell275stem-celldifferentiationtransplantationregenerationtreatment422Results2.111βT21[2]12.1.11TMHC-βCD8+β[3]1[4]2.1.21βFas(CD95)1CD4+CD8+TβCD8+T11CD8+TMHC-CD8+TMHC-1[5]CD4+CD25+T(Treg)T1TT1TT[6]TTTh2[7]TBβT1B2(IA-2)ZnT8βTB1[8]1[9]2.1.3(VNTR)1[10](HLA)1T4(CTLA-4)mRNA[11].1P.O.Box10002,Shenyang110180[12]11[13]2.2.11[14]RezaniaH1PDX-1(pancreaticduodenalhomeobox-1β)PDX-1Kahan[15]Brolen[16]PDX-1PDX-1PDX-1[17]12.2.2ββ[18-19]β[20-21]1βT[22][23]11[9]βCD4+TCD8+TNKCD4+TTh1Th2Th17TregsTh1β212CD8+TTregsSTAT-1βIRF-1Th2410Th1717βTregs1NKNKβCD8+TFasα1.1ISSN2095-4344CN21-1581/RCODEN:ZLKHAH3099[24][25]231[26]Trivedi[27]0.610512.930%50%C426β[28]11Ianus[29]2βVoltarell[30]15173614β615C15137%βTVOLTARELL131315411C3754[31]13[32]Morimoto[33]ββ1PDX-1PDX-1PDX-1[34]PDX-1[35]1(non-obesediabeticNOD)PDX-1PDX-124hNODPDX-1[36]β1Ende[37]21Haller[38]151121512.2.3Barnur[39]β14.5%1Kuise[40]KIF4SOX2OCT4.1P.O.Box10002,Shenyang110180β[41][42]2.3β1123Conclusionandoutlook111ββPDX-1(pancreaticduodenalhomeobox-1)βDNA4References[1]El-ZinyMA,SalemNA,El-HawaryAK,etal.Epidemiologyofchildhoodtype1diabetesmellitusinNileDelta,northernEgypt-aretrospectivestudy.JClinResPediatrEndocrinol.2014;6(1):9-15.[2]vanBelleTL,CoppietersKT,vonHerrathMG.Type1diabetes:etiology,immunology,andtherapeuticstrategies.PhysiolRev.2011;91(1):79-118.[3]ZókaA,SomogyiA,FirneiszG.Type1diabetesmellitus:mostrecentadvancesinitspathogenesisandtreatment.OrvHetil.2012;153(27):1047-1056.[4]PatelarouE,GirvalakiC,BrokalakiH,etal.Currentevidenceontheassociationsofbreastfeeding,infantformula,andcow'smilkintroductionwithtype1diabetesmellitus:asystematicreview.NutrRev.2012;70(9):509-519.[5]MorranMP,VonbergA,KhadraA,etal.Immunogeneticsoftype1diabetesmellitus.MolAspectsMed.2015;42:42-60.[6]MartinezPJ,MathewsC,ActorJK,etal.ImpairedCD4+andT-helper17cellmemoryresponsetoStreptococcuspneumoniaeisassociatedwithelevatedglucoseandpercentglycatedhemoglobinA1cinMexicanAmericanswithtype2diabetesmellitus.TranslRes.2014;163(1):53-63.[7]MichalekJ,VrabelovaZ,HrotekovaZ,etal.ImmuneregulatoryTcellsinsiblingsofchildrensufferingfromtype1diabetesmellitus.ScandJImmunol.2006;64(5):531-535.[8]SzablewskiL.Roleofimmunesystemintype1diabetesmellituspathogenesis.IntImmunopharmacol.20