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《Vascularized and functional human liver from an iPSC-derived organ bud transplant (1)》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
1、LETTERdoi:10.1038/nature12271VascularizedandfunctionalhumanliverfromaniPSC-derivedorganbudtransplant1,2111111TakanoriTakebe,KeisukeSekine,MasahiroEnomura,HiroyukiKoike,MasakiKimura,TakunoriOgaeri,Ran-RanZhang,111,3441,2YasuharuUeno,Yun-WenZheng,NaotoKoi
2、ke,ShinsukeAoyama,YasuhisaAdachi&HidekiTaniguchiAcriticalshortageofdonororgansfortreatingend-stageorganfailuretwo-dimensionalconditions,humaniPSC-HEsself-organizedintohighlightstheurgentneedforgeneratingorgansfromhumaninducedmacroscopicallyvisiblethree-
3、dimensionalcellclustersbyanintrinsic1pluripotentstemcells(iPSCs).Despitemanyreportsdescribingfunc-organizingcapacityupto48hafterseeding(Fig.1b,c,Supplementary2–4tionalcelldifferentiation,nostudieshavesucceededingeneratingathree-dimensionalvascularizedor
4、gansuchasliver.HereweshowtheaHumanEctopictransplantationiPSC-HEsintoimmunodeficientmicegenerationofvascularizedandfunctionalhumanliverfromhumanHepaticHumanspecificationRecapitulationofSelf-organizationintoiPSCsbytransplantationofliverbudscreatedinvitro(
5、iPSC-LBs).iPSCsorganogeneticinteractionsthree-dimensionalliverbudSpecifiedhepaticcells(immatureendodermalcellsdestinedtotrackHumanMSCs4–6-daycultureBloodthehepaticcellfate)self-organizedintothree-dimensionaliPSC-LBsCraniumperfusionMesenterybyrecapitulat
6、ingorganogeneticinteractionsbetweenendothelialandHUVECsSubcapsularbmesenchymalcells5.Immunostainingandgene-expressionanalyses0h12h24h36h72hrevealedaresemblancebetweeninvitrogrowniPSC-LBsandinvivoliverbuds.HumanvasculaturesiniPSC-LBtransplantsbecamefunc-
7、tionalbyconnectingtothehostvesselswithin48hours.Theforma-cdtionoffunctionalvasculaturesstimulatedthematurationofiPSC-LBsintotissueresemblingtheadultliver.HighlymetaboliciPSC-derivedtissueperformedliver-specificfunctionssuchasproteinproductionandhuman-sp
8、ecificdrugmetabolismwithoutrecipientliverreplace-6humanMSCment.Furthermore,mesenterictransplantationofiPSC-LBsrescuedthedrug-inducedlethalliverfailuremodel.Toourknowledge,thisisHumaniPSC-HEHUVECthefirstreportdemonstratingthegener
