CD34+M-cadherin+ Bone Marrow Progenitor Cells Promote Arteriogenesis in Ischemic Hindlimbs of ApoE？？ Mice 英文参考文献.docVIP

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CD34+M-cadherin+ Bone Marrow Progenitor Cells Promote Arteriogenesis in Ischemic Hindlimbs of ApoE？？ Mice 英文参考文献.doc

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CD34M-cadherinBoneMarrowProgenitorCellsPromoteArteriogenesisinIschemicHindlimbsofApoE？？Mice英文参考文献

CD34+/M-cadherin+BoneMarrowProgenitorCells PromoteArteriogenesisinIschemicHindlimbsof 2/2 ApoE Mice ToyaTerry1.,ZhiqiangChen2.,RichardA.F.Dixon1,PeterVanderslice1,PierreZoldhelyi1,JamesT. Willerson1,2,QiLiu1* 1TheTexasHeartInstituteatSt.Luke’sEpiscopalHospital,Houston,Texas,UnitedStatesofAmerica,2TheUniversityofTexasHealthScienceCenter,Houston,Texas, UnitedStatesofAmerica Abstract Background:Cell-basedtherapyshowspromiseintreatingperipheralarterialdisease(PAD);however,theoptimalcelltype andlong-termefficacyareunknown.Inthisstudy,weidentifiedanovelsubpopulationofadultprogenitorcellspositivefor CD34 and M-cadherin (CD34+/M-cad+ BMCs) in mouse and human bone marrow. We also examined the long-lasting therapeutic efficacy of mouse CD34 /M-cad+ BMCs in restoring blood flow and promoting vascularization in an atheroscleroticmousemodelofPAD. + Methods and Findings: Colony-forming cell assays and flow cytometry analysis showed that CD34+/M-cad+ BMCs have + hematopoieticprogenitorproperties.Whendeliveredintra-arteriallyintotheischemichindlimbsofApoE2/2mice,CD34 / + cad BMCs, or unselected BMCs. Significantly more arterioles were seen in CD34 /M-cad+ cell-treated limbs than in any + M-cad BMCsalleviatedischemiaandsignificantlyimprovedbloodflowcomparedwithCD34 /M-cad2 BMCs,CD342/M- + + other treatment group 60 days after cell therapy. Furthermore, histologic assessment and morphometric analyses of hindlimbstreatedwithGFP CD34 /M-cad+cellsshowedthatinjectedcellsincorporatedintosolidtissuestructuresat21 + + days. Confocal microscopic examination of GFP CD34 /M-cad+ cell-treated ischemic legs followed by immunostaining + + indicatedthevasculardifferentiationofCD34+/M-cad+progenitorcells.AcytokineantibodyarrayrevealedthatCD34 /M- + + cad cell-conditionedmediumcontainedhigherlevelsofcytokinesinauniquepattern,includingbFGF,CRG-2,EGF,Flt-3 + ligand,IGF-1,SDF-1,andVEGFR-3,thandidCD34 /M-cad2cell-conditionedmedium.Theproangiogeniccytokinessecreted byCD34 /M-c