Adenoviral Transduction of Mesenchymal Stem Cells In Vitro Responses and In Vivo Immune Responses after Cell Transplantation 英文参考文献.docVIP
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Adenoviral Transduction of Mesenchymal Stem Cells In Vitro Responses and In Vivo Immune Responses after Cell Transplantation 英文参考文献
AdenoviralTransductionofMesenchymalStemCells:In
VitroResponsesandInVivoImmuneResponsesafter
CellTransplantation
OliverTreacy1,AideenE.Ryan1,TeresaHeinzl1,LisaO’Flynn1,MareseCregg1,MieszkoWilk1,
FrancescaOdoardi2,PaulLohan1,TimothyO’Brien1,MikhailNosov1.,ThomasRitter1*.
1CollegeofMedicine,NursingandHealthSciences,SchoolofMedicine,RegenerativeMedicineInstitute,NationalUniversityofIreland,Galway,Ireland,2Institutefor
Multiple-SclerosisResearch,DepartmentofNeuroimmunology,UniversityMedicine,Go¨ttingen,Germany
Abstract
Adultmesenchymalstemcells(MSCs)arenon-hematopoieticcellswithmulti-lineagepotentialwhichmakesthemattractive
targets for regenerative medicine applications. However, to date, therapeutic success of MSC-therapy is limited and the
genetic modification of MSCs using viral vectors is one option to improve their therapeutic potential. Ex-vivo genetic
modificationofMSCsusingrecombinantadenovirus(Ad)couldbepromisingtoreduceundesiredimmuneresponsesasAd
willberemovedbeforecell/tissuetransplantation.Inthisregard,weinvestigatedwhetherAd-modificationofMSCsalters
theirimmunologicalpropertiesinvitroandinvivo.WefoundthatAd-transductionofMSCsdoesnotleadtoup-regulation
ofmajorhistocompatibilitycomplexclassIandIIandco-stimulatorymoleculesCD80andCD86.Moreover,Ad-transduction
causednosignificantchangesintermsofpro-inflammatorycytokineexpression,chemokineandchemokinereceptorand
Toll-like receptor expression. In addition, Ad-modification of MSCs had no affect on their ability to suppress T cell
proliferation in vitro. In vivo injection of Ad-transduced MSCs did not change the frequency of various immune cell
populations(antigenpresentingcells,ThelperandcytotoxicTcells,naturalkillerandnaturalkillerTcells)neitherinthe
bloodnorintissues.OurresultsindicatethatAd-modificationhasnomajorinfluenceontheimmunologicalpropertiesof
MSCsandthereforecanbeconsideredasasuitablegenevectorfortherapeuticapplicationsofMSCs.
Citation: Treacy O, Ryan AE, Heinzl T, O’Flynn L, Cregg M, et al. (2012) Ad
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