保护牙髓组织脱落
- 格式:pdf
- 大小:2.62 MB
- 文档页数:15
CryopreservedDentalPulpTissuesofExfoliatedDeciduousTeethIsaFeasibleStemCellResourceforRegenerativeMedicine
LanMa1,2.,YusukeMakino1.,HaruyoshiYamaza2,KentaroAkiyama3,YoshihiroHoshino2,GuangtaiSong4,ToshioKukita1,KazuakiNonaka2,SongtaoShi3,TakayoshiYamaza1*
1DepartmentofMolecularCellBiologyandOralAnatomy,GraduateSchoolofDentalScience,KyushuUniversity,Fukuoka,Japan,2DepartmentofPediatricDentistry,GraduateSchoolofDentalScience,KyushuUniversity,Fukuoka,Japan,3CenterforCraniofacialMolecularBiology,HermanOstrowSchoolofDentistryofUSC,UniversityofSouthernCalifornia,LosAngeles,California,UnitedStatesofAmerica,4DepartmentofPedodontics,SchoolofStomatology,WuhanUniversity,Wuhan,China
AbstractHumanexfoliateddeciduousteethhavebeenconsideredtobeapromisingsourceforregenerativetherapybecausetheycontainuniquepostnatalstemcellsfromhumanexfoliateddeciduousteeth(SHED)withself-renewalcapacity,multipotencyandimmunomodulatoryfunction.Howeverpreservationtechniqueofdeciduousteethhasnotbeendeveloped.ThisstudyaimedtoevaluatethatcryopreserveddentalpulptissuesofhumanexfoliateddeciduousteethisaretrievableandpracticalSHEDsourceforcell-basedtherapy.SHEDisolatedfromthecryopreserveddeciduouspulptissuesforover2years(25–30months)(SHED-Cryo)ownedsimilarstemcellpropertiesincludingclonogenicity,self-renew,stemcellmarkerexpression,multipotency,invivotissueregenerativecapacityandinvitroimmunomodulatoryfunctiontoSHEDisolatedfromthefreshtissues(SHED-Fresh).ToexaminethetherapeuticefficacyofSHED-Cryoonimmunediseases,SHED-Cryowereintravenouslytransplantedintosystemiclupuserythematosus(SLE)modelMRL/lprmice.SystemicSHED-Cryo-transplantationimprovedSLE-likedisordersincludingshortlifespan,elevatedautoantibodylevelsandnephritis-likerenaldysfunction.SHED-Cryoamendedincreasedinterleukin17-secretinghelperTcellsinMRL/lprmicesystemicallyandlocally.SHED-Cryo-transplantationwasalsoabletorecoverosteoporosisbonereductioninlongbonesofMRL/lprmice.Furthermore,SHED-Cryo-mediatedtissueengineeringinducedboneregenerationincriticalcalvarialbone-defectsitesofimmunocompromisedmice.ThetherapeuticefficacyofSHED-CryotransplantationonimmuneandskeletaldisorderswassimilartothatofSHED-Fresh.Thesedatasuggestthatcryopreservationofdentalpulptissuesofdeciduousteethprovideasuitableanddesirableapproachforstemcell-basedimmunetherapyandtissueengineeringinregenerativemedicine.
Citation:MaL,MakinoY,YamazaH,AkiyamaK,HoshinoY,etal.(2012)CryopreservedDentalPulpTissuesofExfoliatedDeciduousTeethIsaFeasibleStemCellResourceforRegenerativeMedicine.PLoSONE7(12):e51777.doi:10.1371/journal.pone.0051777
Editor:NielsOlsenSaraivaCaˆmara,UniversidadedeSaoPaulo,BrazilReceivedJuly8,2012;AcceptedNovember12,2012;PublishedDecember14,2012Copyright:ß2012Maetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.
Funding:ThisworkwassupportedbythegrantsfromMinistryofEducation,Culture,Sports,ScienceandTechnologyofJapanforChallengingExploratoryResearchProject(no.24659815toTYandno.23659967toKN)andforYoungScientists(B)(no.20790260toHY)ofJapanSocietyforPromotionofScienceandfromNationalInstituteofDentalandCraniofacialResearch,NationalInstitutesofHealth,DepartmentofHealthandHumanServices,USA(R01DE17449andR01DE019156toSS).Thefundershadnoroleinstudydesign,datacollectionandanalysis,decisiontopublish,orpreparationofthemanuscript.
CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist.*E-mail:yamazata@dent.kyushu-u.ac.jp.Theseauthorscontributedequallytothiswork.
IntroductionMesenchymalstemcells(MSCs)havebeenisolatedfromavarietyoffetalandadulttissuesandconsideredasanidealcandidatesourceforcell-basedtherapyduetotheiruniquepropertiessuchasmultipotencyandimmunomodulatoryfunctions[1].ManyresearchershaveinvestigatedtoapplyMSCsasprogenitorsofosteoblastsforbonetissueengineering.ClinicalevidencessupporttheefficacyofMSC-basedskeletaltissueregeneration[2,3].Ontheotherhand,MSCsexertstrikingregulatoryeffectsonimmunecellssuchasT-andB-lymphocytes,dendriticcellsandnaturalkillercells[4,5].ThisimmunologicaltraitsofMSCsleadtotakeclinicaladvantagestoimmunediseasessuchasacutegraft-versus-host-disease(GVHD)[4,6],hematopoi-eticstemcell(HSC)engraftment[7,8]andsystemiclupuserythematosus(SLE)[9].
RecentdiscoveryhasevaluatedthatfreshdentalpulptissuesofhumanexfoliateddeciduousteethpreserveMSCpopulation,termedSHED[10].SHEDdisplaytypicalstemcellpropertiesincludingclonogenicity,cellproliferationandmultipotencytodifferentiateintoodontoblast/osteoblast-,adipocyte-,andneuralcell-likecells[10].SHEDalsoexpressauniqueinvivotissueregenerationcapabilityofformingdentin/pulpandbone/bonemarrowstructureswhensubcutaneouslytransplantedintoimmu-nocompromisedmice[10].SHEDimplantationgovernbonerepairincritical-sizedbonedefectsinmousecalvarias[11]andswinemandible[12].Moreover,systemicSHED-transplantationexhibitedeffectiveimprovementonSLE-likedisordersincludinghyper-autoantibodylevels,renaldysfunctionandhyperactivityofinterleukin17(IL-17)-producinghelperT(Th17)cells,inMRL/lprmice[13].ThereforeSHEDareconsideredtobeafeasibleand