Ex Vivo Expansion of Human Hematopoietic Stem Cells by Garcinol, a Potent Inhibitor of Histone Acetyltransferase 英文参考文献.docVIP

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Ex Vivo Expansion of Human Hematopoietic Stem Cells by Garcinol, a Potent Inhibitor of Histone Acetyltransferase 英文参考文献.doc

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Ex Vivo Expansion of Human Hematopoietic Stem Cells by Garcinol, a Potent Inhibitor of Histone Acetyltransferase 英文参考文献

ExVivoExpansionofHumanHematopoieticStemCells byGarcinol,aPotentInhibitorofHistone Acetyltransferase TaitoNishino1,ChangshanWang2,4,MakikoMochizuki-Kashio2,4,MitsujiroOsawa2,4 ,Hiromitsu Nakauchi3,5,AtsushiIwama2,4 * 1Research Planning Department, Nissan Chemical Industries, Tokyo, Japan, 2Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University,Chiba,Japan,3DivisionofStemCellTherapy,CenterforStemCellBiologyandRegenerativeMedicine,InstituteofMedicalScience,UniversityofTokyo,Tokyo, Japan,4JapanScienceandTechnologyAgency,CREST,Tokyo,Japan,5ERATO,Tokyo,Japan Abstract Background: Human cord blood (hCB) is the main source of hematopoietic stem and progenitor cells (HSCs/PCs) for transplantation.EffortstoovercomerelativeshortagesofHSCs/PCshaveledtotechnologiestoexpandHSCs/PCsexvivo. However,methodssuitableforclinicalpracticehaveyettobefullyestablished. Methodology/Principal Findings: In this study, we screened biologically active natural products for activity to promote expansionofhCBHSCs/PCsexvivo,andidentifiedGarcinol,aplant-derivedhistoneacetyltransferase(HAT)inhibitor,asa + novelstimulatorofhCBHSC/PCexpansion.Duringa7-daycultureofCD34 CD38–HSCssupplementedwithstemcellfactor + – andthrombopoietin,GarcinolincreasednumbersofCD34 CD38 HSCs/PCsmorethan4.5-foldandIsogarcinol,aderivative of Garcinol, 7.4-fold. Furthermore, during a 7-day culture of CD34+ HSCs/PCs, Garcinol expanded the number of SCID- repopulatingcells(SRCs)2.5-fold.WealsodemonstratedthatthecapacityofGarcinolanditsderivativestoexpandHSCs/ PCswascloselycorrelatedwiththeirinhibitoryeffectonHAT.TheGarcinolderivativeswhichexpandedHSCs/PCsinhibited theHATactivityandacetylationofhistones,whileinactivederivativesdidnot. Conclusions/Significance:OurfindingsidentifyGarcinolasthefirstnaturalproductactingonHSCs/PCsandsuggestthe inhibitionofHATtobeanalternativeapproachformanipulatingHSCs/PCs. Citation:NishinoT,WangC,Mochizuki-KashioM,OsawaM,NakauchiH,etal.(2011)ExVivoExpansiono