Mesenchymal Stem Cell 1 (MSC1)-Based Therapy Attenuates Tumor Growth Whereas MSC2-Treatment Promotes Tumor Growth and Metastasis 英文参考文献.docVIP

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Mesenchymal Stem Cell 1 (MSC1)-Based Therapy Attenuates Tumor Growth Whereas MSC2-Treatment Promotes Tumor Growth and Metastasis 英文参考文献.doc

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Mesenchymal Stem Cell 1 (MSC1)-Based Therapy Attenuates Tumor Growth Whereas MSC2-Treatment Promotes Tumor Growth and Metastasis 英文参考文献

MesenchymalStemCell1(MSC1)-BasedTherapy AttenuatesTumorGrowthWhereasMSC2-Treatment PromotesTumorGrowthandMetastasis RuthS.Waterman1,SarahL.Henkle2,AlineM.Betancourt2,3* 1DepartmentofAnesthesiology,OchsnerClinicFoundation,NewOrleans,Louisiana,UnitedStatesofAmerica,2TulaneCenterforStemCellResearchandRegenerative Medicine,TulaneUniversitySchoolofMedicine,NewOrleans,Louisiana,UnitedStatesofAmerica,3DepartmentofMedicine,TulaneUniversitySchoolofMedicine,New Orleans,Louisiana,UnitedStatesofAmerica Abstract Background:Currently,therearemanypromisingclinicaltrialsusingmesenchymalstemcells(MSCs)incell-basedtherapies ofnumerousdiseases.Increasingly,however,thereisaconcernovertheuseofMSCsbecausetheyhometotumorsandcan support tumor growth and metastasis. For instance, we established that MSCs in the ovarian tumor microenvironment promotedtumorgrowthandfavoredangiogenesis.Inparallelstudies,wealsodevelopedanewapproachtoinducethe conventionalmixedpoolofMSCsintotwouniformbutdistinctphenotypeswetermedMSC1andMSC2. Methodology/PrincipalFindings:HerewetestedtheinvitroandinvivostabilityofMSC1andMSC2phenotypesaswellas theireffectsontumorgrowthandspread.Invitroco-cultureofMSC1withvariouscancercellsdiminishedgrowthincolony forming units and tumor spheroid assays, while conventional MSCs or MSC2 co-culture had the opposite effect in these assays.Co-cultureofMSC1andcancercellsalsodistinctlyaffectedtheirmigrationandinvasionpotentialwhencomparedto MSCs or MSC2 treated samples. The expression of bioactive molecules also differed dramatically among these samples. MSC1-basedtreatmentofestablishedtumorsinanimmunecompetentmodelattenuatedtumorgrowthandmetastasisin contrasttoMSCs-andMSC2-treatedanimalsinwhichtumorgrowthandspreadwasincreased.Also,incontrasttothese groups, MSC1-therapy led to less ascites accumulation, increased CD45+leukocytes, decreased collagen deposition, and mastcelldegranulation. Conclusion/Significance:TheseobservationsindicatethattheMSC1andMSC2phenotypesmaybeconvenienttoolsfor