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1、LETTERdoi:10.1038/nature12271VascularizedandfunctionalhumanliverfromaniPSC-derivedorganbudtransplant1,2111111TakanoriTakebe,KeisukeSekine,MasahiroEnomura,HiroyukiKoike,MasakiKimura,TakunoriOgaeri,Ran-RanZhang,111,3441,2YasuharuUeno,Yun-WenZheng,NaotoKoike,ShinsukeAoyama,Yasuhis
2、aAdachi&HidekiTaniguchiAcriticalshortageofdonororgansfortreatingend-stageorganfailuretwo-dimensionalconditions,humaniPSC-HEsself-organizedintohighlightstheurgentneedforgeneratingorgansfromhumaninducedmacroscopicallyvisiblethree-dimensionalcellclustersbyanintrinsic1pluripotentst
3、emcells(iPSCs).Despitemanyreportsdescribingfunc-organizingcapacityupto48hafterseeding(Fig.1b,c,Supplementary2–4tionalcelldifferentiation,nostudieshavesucceededingeneratingathree-dimensionalvascularizedorgansuchasliver.HereweshowtheaHumanEctopictransplantationiPSC-HEsintoimmunod
4、eficientmicegenerationofvascularizedandfunctionalhumanliverfromhumanHepaticHumanspecificationRecapitulationofSelf-organizationintoiPSCsbytransplantationofliverbudscreatedinvitro(iPSC-LBs).iPSCsorganogeneticinteractionsthree-dimensionalliverbudSpecifiedhepaticcells(immatureendod
5、ermalcellsdestinedtotrackHumanMSCs4–6-daycultureBloodthehepaticcellfate)self-organizedintothree-dimensionaliPSC-LBsCraniumperfusionMesenterybyrecapitulatingorganogeneticinteractionsbetweenendothelialandHUVECsSubcapsularbmesenchymalcells5.Immunostainingandgene-expressionanalyses
6、0h12h24h36h72hrevealedaresemblancebetweeninvitrogrowniPSC-LBsandinvivoliverbuds.HumanvasculaturesiniPSC-LBtransplantsbecamefunc-tionalbyconnectingtothehostvesselswithin48hours.Theforma-cdtionoffunctionalvasculaturesstimulatedthematurationofiPSC-LBsintotissueresemblingtheadultli
7、ver.HighlymetaboliciPSC-derivedtissueperformedliver-specificfunctionssuchasproteinproductionandhuman-specificdrugmetabolismwithoutrecipientliverreplace-6humanMSCment.Furthermore,mesenterictransplantationofiPSC-LBsrescuedthedrug-inducedlethalliverfailuremodel.Toourknowledge,this
8、isHumaniPSC-HEHUVECthefirstreportdemonstratingthegener
