Immunogenicity of induced pluripotent stem cells.pdf

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1、LETTERdoi:10.1038/nature10135Immunogenicityofinducedpluripotentstemcells1111TongbiaoZhao,Zhen-NingZhang,ZhiliRong&YangXuInducedpluripotentstemcells(iPSCs),reprogrammedfromso-iPSCclones,tworeprogrammedwiththreefactors(V3-1andV3-3)maticcellswithdefinedfactors,holdgreatpromiseforregenerativeandtwowi

2、thfourfactors(V4-1andV4-2),wereselectedforfurther1–5medicineastherenewablesourceofautologouscells.Whereasitanalysis(SupplementaryFig.2h).MostimplantedB6ViPSCsfailedtohasbeengenerallyassumedthattheseautologouscellsshouldbeformdetectableteratomasorformedteratomasthatweresubsequentlyimmune-tolerated

3、bytherecipientfromwhomtheiPSCsareimmune-rejectedwithTcellinfiltrationandmassivenecrosis(Sup-derived,theirimmunogenicityhasnotbeenvigorouslyexamined.plementaryFig.3a–e).Theteratomasthatdidnotundergoapparent1Weshowherethat,whereasembryonicstemcells(ESCs)derivedregressionwerealsoinfiltratedwithCD4Tc

4、ellswithapparentfrominbredC57BL/6(B6)micecanefficientlyformteratomasinB6micewithoutanyevidentimmunerejection,theallogeneicESCsafrom129/SvJmicefailtoformteratomasinB6miceduetorapidrejectionbyrecipients.B6mouseembryonicfibroblasts(MEFs)werereprogrammedintoiPSCsbyeitherretroviralapproach(ViPSCs)oran

5、ovelepisomalapproach(EiPSCs)thatcausesnogenomicintegration.IncontrasttoB6ESCs,teratomasformedbyB6ViPSCsweremostlyimmune-rejectedbyB6recipients.Inaddition,themajorityofteratomasformedbyB6EiPSCswereimmunogenicinB6micewithTcellinfiltration,andapparenttissuedamageandregressionwereobservedinasmallfrac

6、tionofteratomas.GlobalgeneexpressionanalysisofteratomasformedbyB6129B6129B6ESCsandEiPSCsrevealedanumberofgenesfrequentlyover-bcexpressedinteratomasderivedfromEiPSCs,andseveralsuchgeneCellline(number)Day21(%)Day30(%)productswereshowntocontributedirectlytotheimmunogenicityC57BL/6(1x106)12/12(100)18

7、/19(95)*oftheB6EiPSC-derivedcellsinB6mice.Thesefindingsindicate(3x106)–12/12(100)that,incontrasttoderivativesofESCs,abnormalgeneexpressionin129(1x106)0/12(0)0/19(0)(3x106)–1*/12(8.3)somecellsdifferentiatedfromiPSCscani