彤干细胞治疗视网膜变性疾病研究进展

视网膜变性：获得性(AMD(RP)1946,immaturetissueforreplacement. StemCells胚胎干细胞,ESCells 胚胎生殖细胞,EGCellsFetal–胎儿组织、脐血干细胞、 Tissue Adult–ADSC（脂肪干细胞 BMSC（骨髓间充质干细胞）直接移植或分化UC-MSC（脐带间充质干细胞）直接移植或分化 A-H,surfacemarkers;I,markersforRPEvsSC;J,PhagocytosisofPhRodobioparticles;K,

SurvivalandintegrationofhESC-RPEintoanmouseeye(9M)stainedwithanti-hmitochondria(A)andanti-hbestrophinInclusionandexclusioncriteria:end-stagedisease,centralvisualloss,theabsenceofothersignificantophthalmicpathologicaleffects,acancer-freemedicalhistory,presentcancerscreening,theabsenceofcontraindicationsimmuno-suppression,(surgery…),psychologicalsuitabilitytoparticipateinafirst-in-humanclinicaltrialinvolvinghESC-derivedtransplanttissue.ClinicaltrialwithES-derivedRPEinmaculardegenerationIncreased DecreasedIncreased Decreased8/18>15Atrophic Cells:ESC-derivedRPEcells50,000;100,000;150,000Amedianof22monthsUpto37monthsNoadverseproliferationNorejectionNoseriousocularNosystemicsafetyGraft13/18,subretinalPigmentedpreretinalgrowthswereseenineyes.Thefundusphoto/OCTshowasmallpigmentedclump,perhapsasinglecell,inapatientwithStargardt'sdisease1Mafter20140912:FirstiPSC-RPE

Firstinducedretinalprogenitorcells.Ikedaetal.,PNAS2005;102:11331-11336MFirstinducedphotoreceptorandfunctionalRPEcell.Osakada,Ikeda,etal.,NatBiotechnol2008;26:215-24FirstinductionofPRandRPEcellwithsmallmoleculesOsakada,Jin,etalMFirstnon-integratedhiPSintoPRandRPEcells.Jinetal.,StemCellsTranslMed2012;1(6):503-TimingisDonorcellscanintegrateintotheadultordegeneratingretinaiftheyaretakenfromthedevelopingretinaatatimecoincidentwiththepeakofrodgenesis.Successfullyintegratedrodphotoreceptorsarederivedonlyfromimmaturepost-mitoticrodprecursorsandnotfromproliferatingprogenitororstemcells.Thesefindingsdefinetheontogeneticstageofdonorcellsforsuccessfulrodphotoreceptortransplantation.0000000

JCI (MSC)ADSCs/BMSCs:QuestionstoCriteriaforidealdonorcellsforDegenerativeRetinalDiseases(Himesetal.NeurorehabilNeuralRepair2006;20:278-96)IfhADSCs/BMSCssatisfyallthecriteria+below Multipotent,ExpressingMSC Cansurvive,migrate,integrateorevendifferentiateafter Sustainingvisionwithoutprovokingabnormal Secretingcytokinesandgrowth Havingreceptorstoabsorbexcessunwanted Obtainableinlargeamountforsafety Easilyaccessibleforclinicalusew/omajorpreparativeCultureinCultureinIsolation/CultureofthecellsandCultureinCultureinfromfemur a,b)大鼠骨a,b)大鼠骨白；i)源于MSCsMSCsareusedtotreatClin&ExpOphthal.2008;IOVS.2007;ExpEyeRes.2010;ExpEyeRes.2007;CurMolMed.2013;13:1-DifferentialdifferentiationcapacitiesofMSCDifferentiationofCD90+ratBMSCintophotoreceptorsintheRCSratGFP-CD90+rat CD90+ratInsubretinal

CoexpressionofGFP(green)andOpsin(red)TheJournalofNeuroscience,2003•IdentificationandisolationofMSCSinglecellExperimentalHema