Adult Pancreas Side Population Cells Expand after β Cell Injury and Are a Source of Insulin-Secreting Cells 英文参考文献.docVIP

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Adult Pancreas Side Population Cells Expand after β Cell Injury and Are a Source of Insulin-Secreting Cells 英文参考文献.doc

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Adult Pancreas Side Population Cells Expand after β Cell Injury and Are a Source of Insulin-Secreting Cells 英文参考文献

AdultPancreasSidePopulationCellsExpandafterbCell InjuryandAreaSourceofInsulin-SecretingCells IliaBanakh1,2,LeonelJ.Gonez1,2,RobynM.Sutherland1,2,GaetanoNaselli1,2,LeonardC.Harrison1,2 * 1TheWalterandElizaHallInstituteofMedicalResearch,Parkville,Victoria,Australia,2DepartmentofMedicalBiology,TheUniversityofMelbourne,Parkville,Victoria, Australia Abstract Pancreasstemcellsareapotentialsourceofinsulin-producingbcellsforthetherapyofdiabetes.Inadulttissuesthe‘side population’(SP)ofcellsthateffluxestheDNAbindingdyeHoechst33342throughATP-bindingcassettetransportershas stem cell properties. We hypothesised therefore that the SP would expand in response to b cell injury and give rise to functional b cells. SP cells were flow sorted from dissociated pancreas cells of adult mice, analysed for phenotype and culturedwithgrowthpromotinganddifferentiationfactorsbeforeanalysisforhormoneexpressionandglucose-stimulated insulinsecretion.SPcellnumberandcolonyformingpotential(CFP)increasedsignificantlyinmodelsoftypediabetes,and afterpartialpancreatectomy,intheabsenceofhyperglycaemia.SPcells,,1%oftotalpancreascellsat1weekofage,were enriched .10-fold for CFP compared to non-SP cells. Freshly isolated SP cells contained no insulin protein or RNA but expressedthehomeoboxtranscriptionfactorPdx1requiredforpancreasdevelopmentandbcellfunction.Pdx1,alongwith surfaceexpressionofCD326(Ep-Cam),wasamarkerofthecolonyformingandproliferationpotentialofSPcells.Inserum- freemediumwithdefinedfactors,SPcellsproliferatedanddifferentiatedintoislethormone-expressingcellsthatsecreted insulin in response to glucose. Insulin expression was maintained when tissue was transplanted within vascularised chambersintodiabeticmice.SPcellsintheadultpancreasexpandinresponsetobcellinjuryandareasourceofbcell progenitorswithpotentialforthetreatmentofdiabetes. Citation:BanakhI,GonezLJ,SutherlandRM,NaselliG,HarrisonLC(2012)AdultPancreasSidePopulationCellsExpandafterbCellInjuryandAreaSourceof Insulin-SecretingCells.PLoSONE7(1