Bone Marrow Mesenchymal Stem Cells for Improving Hematopoietic Function An In Vitro and In Vivo Model. Part 2 Effect on Bone Marrow Microenvironment 英文参考文献.docVIP

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Bone Marrow Mesenchymal Stem Cells for Improving Hematopoietic Function An In Vitro and In Vivo Model. Part 2 Effect on Bone Marrow Microenvironment 英文参考文献.doc

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Bone Marrow Mesenchymal Stem Cells for Improving Hematopoietic Function An In Vitro and In Vivo Model. Part 2 Effect on Bone Marrow Microenvironment 英文参考文献

BoneMarrowMesenchymalStemCellsforImproving HematopoieticFunction:AnInVitroandInVivoModel. Part2:EffectonBoneMarrowMicroenvironment SorayaCarrancio1,2,3,BelenBlanco1,2,3,CarlosRomo1,2,3,SandraMuntion1,2,NataliaLopez-Holgado1,2 JuanF.Blanco4,JesusG.Brin?on5,JesusF.SanMiguel1,2,3,FerminM.Sanchez-Guijo1,2,M.Consuelodel , Can?izo1,2,3 * 1ServiciodeHematolog?′a,HospitalUniversitariodeSalamanca,Salamanca,Spain,2CentroenReddeMedicinaRegenerativayTerapiaCelulardeCastillayLeo′nandRed Nacional de Terapia Celular (Tercel, ISCIII), Castilla y Leo′n, Spain, 3Centro de Investigacio′n del Ca′ncer-IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain, 4ServiciodeTraumatolog?′a,HospitalUniversitariodeSalamanca,Salamanca,Spain,5DepartamentodeBiologiaCelularyPatologia,UniversidaddeSalamanca,Spain Abstract Theaimofthepresentstudywastodeterminehowmesenchymalstemcells(MSC)couldimprovebonemarrow(BM)stroma functionafterdamage,bothinvitroandinvivo.HumanMSCfrom20healthydonorswereisolatedandexpanded.Mobilized selectedCD34 progenitorcellswereobtainedfrom20HSCTdonors.Forinvitrostudy,long-termbonemarrowcultures + (LTBMC)wereperformedusingaetoposidedamagedstromalmodeltotestMSCeffectinstromalconfluence,capabilityof MSCtolodgeinstromallayeraswellassomemolecules(SDF1,osteopontin,)involvedinhematopoieticnichemaintenance wereanalyzed.Fortheinvivomodel,64NOD/SCIDrecipientsweretransplantedwithCD34+cellsadministeredeitherby intravenous(IV)orintrabone(IB)route,withorwithoutBMderivedMSC.MSClodgementwithintheBMnichewasassessedby FISHanalysisandtheexpressionofSDF1andosteopontinbyimmunohistochemistry.Invivostudyshowedthatwhenthe stromaldamagewassevere,TP-MSCcouldlodgeintheetoposide-treatedBMstroma,asshownbyFISHanalysis.Osteopontin andSDF1weredifferentlyexpressedindamagedstromaandtheirexpressionrestoredafterTP-MSCaddition.Humaninvivo MSClodgementwasobservedwithinBMnichebyFISH,butMSConlyweredetectedandnotinthecontralateralfemurs. HumanMSCwerelocatedaroundbloodvesselsinthesubendoestalregionoffemursandexpress