Augmentation of Neovascularizaiton in Hindlimb Ischemia by Combined Transplantation of Human Embryonic Stem Cells-Derived Endothelial and Mural Cells 英文参考文献.docVIP

Augmentation of Neovascularizaiton in Hindlimb Ischemia by Combined Transplantation of Human Embryonic Stem Cells-Derived Endothelial and Mural Cells 英文参考文献.doc

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Augmentation of Neovascularizaiton in Hindlimb Ischemia by Combined Transplantation of Human Embryonic Stem Cells-Derived Endothelial and Mural Cells 英文参考文献

AugmentationofNeovascularizaitoninHindlimb IschemiabyCombinedTransplantationofHuman EmbryonicStemCells-DerivedEndothelialandMural Cells KenichiYamahara1.,MasakatsuSone1.,HiroshiItoh1,2*,JunK.Yamashita3,TakamiYurugi-Kobayashi3, KoichiroHomma2,Ting-HsingChao4,KazutoshiMiyashita1,2,KwijunPark1,NaofumiOyamada1 ,Naoya Sawada1,DaisukeTaura1,YasutomoFukunaga1,NaohisaTamura1,KazuwaNakao1 1DepartmentofMedicineandClinicalScience,KyotoUniversityGraduateSchoolofMedicine,Kyoto,Japan,2DepartmentofInternalMedicine,KeioUniversitySchoolof Medicine, Tokyo, Japan, 3Laboratory of Stem Cell Differentiation, Stem Cell Research Center, Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan, 4DivisionofCardiology,DepartmentofInternalMedicine,NationalChengKungUniversityMedicalCenter,Tainan,Taiwan Abstract Background:Wedemonstratedthatmouseembryonicstem(ES)cells-derivedvascularendothelialgrowthfactorreceptor-2 (VEGF-R2)positivecellscoulddifferentiateintobothendothelialcells(EC)andmuralcells(MC),andtermedthemasvascular progenitorcells(VPC).Recently,wehaveestablishedamethodtoexpandmonkeyandhumanEScells-derivedVPCwiththe properdifferentiationstageinalargequantity.HereweinvestigatedthetherapeuticpotentialofhumanVPC-derivedEC andMCforvascularregeneration. MethodsandResults:AftertheexpansionofhumanVPC-derivedvascularcells,wetransplantedthesecellstonudemice withhindlimbischemia.Thebloodflowrecoveryandcapillarydensityinischemichindlimbsweresignificantlyimprovedin human VPC-derived EC-transplanted mice, compared to human peripheral and umbilical cord blood-derived endothelial progenitor cells (pEPC and uEPC) transplanted mice. The combined transplantation of human VPC-derived EC and MC synergistically improved blood flow of ischemic hindlimbs remarkably, compared to the single cell transplantations. TransplantedVPC-derivedvascularcellswereeffectivelyincorporatedintohostcirculatingvesselsasECandMCtomaintain long-termvascularintegrity. Conclusions:Ourfindingssuggestthatthecombinedtran

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