2020
Chemical mutagenesis of a GPCR ligand: Detoxifying “inflammo-attraction” to direct therapeutic stem cell migration
Lee J, Zhang R, Yan M, Duggineni S, Wakeman D, Niles W, Feng Y, Chen J, Hamblin M, Han E, Gonzalez R, Fang X, Zhu Y, Wang J, Xu Y, Wenger D, Seyfried T, An J, Sidman R, Huang Z, Snyder E. Chemical mutagenesis of a GPCR ligand: Detoxifying “inflammo-attraction” to direct therapeutic stem cell migration. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 31177-31188. PMID: 33219123, PMCID: PMC7733796, DOI: 10.1073/pnas.1911444117.Peer-Reviewed Original ResearchConceptsNeural stem cellsCXCR4 agonistPrototypical neurodegenerative diseaseDonor-derived cellsStem cellsCerebral cortexCNS injuryInflammatory chemokinesHost inflammationUndesirable inflammationCXCL-12Mouse modelTherapeutic impactChemokine CXCL12Stem cell propertiesCell engagementNeurodegenerative diseasesStem cell migrationNSC migrationAgonistsSynthetic functionInflammationChemokinesFundamental stem cell propertiesCXCL12Mitomycin-C treatment during differentiation of induced pluripotent stem cell-derived dopamine neurons reduces proliferation without compromising survival or function in vivo
Hiller B, Marmion D, Gross R, Thompson C, Chavez C, Brundin P, Wakeman D, McMahon C, Kordower J. Mitomycin-C treatment during differentiation of induced pluripotent stem cell-derived dopamine neurons reduces proliferation without compromising survival or function in vivo. Stem Cells Translational Medicine 2020, 10: 278-290. PMID: 32997443, PMCID: PMC7848297, DOI: 10.1002/sctm.20-0014.Peer-Reviewed Original ResearchConceptsDopamine neuronsInduced pluripotent stem cellsParkinson's diseaseStem cell-derived dopamine neuronsPD cell therapyMidbrain dopamine neuronsLong-term survivalTransplant of cellsStem cellsHuman induced pluripotent stem cellsPluripotent stem cellsNeuron preparationsMitomycin C treatmentAthymic ratsDrug selectionUndesirable proliferationCell therapyRobust survivalLower proliferationVivo functionNeuronsTransplantationSurvivalProliferative cellsDisease
2017
Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo
Wakeman D, Hiller B, Marmion D, McMahon C, Corbett G, Mangan K, Ma J, Little L, Xie Z, Perez-Rosello T, Guzman J, Surmeier D, Kordower J. Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo. Stem Cell Reports 2017, 9: 149-161. PMID: 28579395, PMCID: PMC5511045, DOI: 10.1016/j.stemcr.2017.04.033.Peer-Reviewed Original ResearchConceptsParkinson's diseaseDopamine neuronsMidbrain dopamine neuronsStem cell therapyGrafted neuronsHost striatumCell-based therapiesPluripotent stem cell therapyFunctional deficitsPrimate modelFiber innervationParkinsonian phenotypeTherapeutic efficacyTransplantation studiesCell therapyNeuronsSignificant reversalTranslational developmentBehavioral assessmentClinical applicationTherapyElectrophysiological signaturesRatsDiseaseMinimal manipulation
2015
Autologous iPSC‐derived dopamine neuron grafts show considerable promise in a nonhuman primate model of Parkinson's disease
Wakeman D. Autologous iPSC‐derived dopamine neuron grafts show considerable promise in a nonhuman primate model of Parkinson's disease. Movement Disorders 2015, 30: 1034-1034. PMID: 26095814, DOI: 10.1002/mds.26267.Peer-Reviewed Original Research
2014
Survival and Integration of Neurons Derived from Human Embryonic Stem Cells in MPTP-Lesioned Primates
Wakeman DR, Weiss S, Sladek JR, Elsworth JD, Bauereis B, Leranth C, Hurley PJ, Roth RH, Redmond DE. Survival and Integration of Neurons Derived from Human Embryonic Stem Cells in MPTP-Lesioned Primates. Cell Transplantation 2014, 23: 981-994. PMID: 23562290, DOI: 10.3727/096368913x664865.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cell linesEmbryonic stem cell linesHuman embryonic stem cellsEmbryonic stem cellsGene expression studiesStem cell linesGFP lentiviral vectorExpression studiesDifferentiated cellsDifferentiation protocolsDopamine neuronal survivalIntegration of neuronsNeuronal cellsNeuronal phenotypeTyrosine hydroxylaseStem cellsExtension of processesBiochemical analysisDopaminergic marker tyrosine hydroxylaseHESCCell linesIII-tubulinMidbrain of MPTPPhenotypeMembrane depolarizationPeripheral alpha‐synuclein and Parkinson's disease
Olanow C, Wakeman D, Kordower J. Peripheral alpha‐synuclein and Parkinson's disease. Movement Disorders 2014, 29: 963-966. PMID: 25043799, DOI: 10.1002/mds.25966.Peer-Reviewed Original ResearchSpecial issue on stem cells
Wakeman D, Kordower J. Special issue on stem cells. The Journal Of Comparative Neurology 2014, 522: 2689-2690. PMID: 24942075, DOI: 10.1002/cne.23611.Peer-Reviewed Original ResearchNeonatal immune-tolerance in mice does not prevent xenograft rejection
Mattis V, Wakeman D, Tom C, Dodiya H, Yeung S, Tran A, Bernau K, Ornelas L, Sahabian A, Reidling J, Sareen D, Thompson L, Kordower J, Svendsen C. Neonatal immune-tolerance in mice does not prevent xenograft rejection. Experimental Neurology 2014, 254: 90-98. PMID: 24440640, PMCID: PMC3954854, DOI: 10.1016/j.expneurol.2014.01.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAnimals, Outbred StrainsCells, CulturedCorpus StriatumDisease Models, AnimalFemaleGraft RejectionGraft SurvivalHeterograftsHumansHuntingtin ProteinHuntington DiseaseImmune ToleranceMaleMiceMice, Inbred NODMice, SCIDMice, TransgenicNerve Tissue ProteinsNeural Stem CellsNuclear ProteinsTransplantation, HeterologousConceptsNeonatal toleranceRapid rejectionHuman stem cell transplantationImmune-intact miceSignificant immune rejectionStem cell transplantationHumanized mouse modelXenograft rejectionCell transplantationRodent modelsMouse modelImmune rejectionMiceConflicting resultsStem cell typesXenograftsRecent reportsCell typesRejectionTransplantationRatsDiseaseHoming of Neural Stem Cells From the Venous Compartment Into a Brain Infarct Does Not Involve Conventional Interactions With Vascular Endothelium
Goncharova V, Das S, Niles W, Schraufstatter I, Wong A, Povaly T, Wakeman D, Miller L, Snyder E, Khaldoyanidi S. Homing of Neural Stem Cells From the Venous Compartment Into a Brain Infarct Does Not Involve Conventional Interactions With Vascular Endothelium. Stem Cells Translational Medicine 2014, 3: 229-240. PMID: 24396034, PMCID: PMC3925049, DOI: 10.5966/sctm.2013-0052.Peer-Reviewed Original ResearchConceptsHuman neural stem cellsNeural stem cellsIntravenous administrationStromal cell-derived factor-1αEx vivo fucosylationCutaneous lymphocyte antigenBlood-brain barrierStem cellsMortality of ratsHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsImplantation of cellsBrain infarctsVein endothelial cellsLymphocyte antigenVascular endotheliumIntracranial injectionVenous compartmentCell surface moietiesFactor-1αIntravascular spaceEndothelial cellsAdministrationLuminal surfaceRemoval of fucose
2011
Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease
Kriks S, Shim J, Piao J, Ganat Y, Wakeman D, Xie Z, Carrillo-Reid L, Auyeung G, Antonacci C, Buch A, Yang L, Beal M, Surmeier D, Kordower J, Tabar V, Studer L. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature 2011, 480: 547-551. PMID: 22056989, PMCID: PMC3245796, DOI: 10.1038/nature10648.Peer-Reviewed Original ResearchCell Transplantation and Gene Therapy in Parkinson's Disease
Wakeman D, Dodiya H, Kordower J. Cell Transplantation and Gene Therapy in Parkinson's Disease. Annals Of Global Health 2011, 78: 126-158. PMID: 21259269, DOI: 10.1002/msj.20233.Peer-Reviewed Original ResearchConceptsParkinson's diseaseLong-term disease modificationFetal dopamine neuronsGraft-induced dyskinesiaStem cell transplantationCourse of diseaseDirect cell replacementProgressive neurodegenerative disorderWidespread clinical useGene therapyPatient-derived cellsDopamine replacementMotor symptomsDisease modificationDopamine deficiencyViral vector deliveryCell transplantationSymptomatic strategiesDopamine neuronsClinical trialsEfficacy profileDopaminergic circuitryMotor neuronsClinical studiesVentral midbrain
2010
Microarray-based Transcriptional and Epigenetic Profiling of Matrix Metalloproteinases, Collagens, and Related Genes in Cancer*
Chernov A, Baranovskaya S, Golubkov V, Wakeman D, Snyder E, Williams R, Strongin A. Microarray-based Transcriptional and Epigenetic Profiling of Matrix Metalloproteinases, Collagens, and Related Genes in Cancer*. Journal Of Biological Chemistry 2010, 285: 19647-19659. PMID: 20404328, PMCID: PMC2885243, DOI: 10.1074/jbc.m109.088153.Peer-Reviewed Original ResearchConceptsEpigenetic profilingGenome-wide transcriptional profilingEpigenetic stimulationCommon epigenetic signaturesStrict epigenetic controlPro-invasive genesMultiple collagen genesBivalent marksQuantitative reverse transcription PCRDevelopmental genesEpigenetic controlMatrix metalloproteinasesTrimethylation marksEpigenetic mechanismsTranscriptional profilingEpigenetic signaturesAdditional genesGlioma cellsH3 hyperacetylationEpigenetic studiesEpigenetic parametersIndividual matrix metalloproteinasesU251 glioma cellsRelated genesReverse transcription-PCRCellular Repair in the Parkinsonian Nonhuman Primate Brain
Redmond DE, Weiss S, Elsworth JD, Roth RH, Wakeman DR, Bjugstad KB, Collier TJ, Blanchard BC, Teng YD, Synder EY, Sladek JR. Cellular Repair in the Parkinsonian Nonhuman Primate Brain. Rejuvenation Research 2010, 13: 188-194. PMID: 20370501, PMCID: PMC2946058, DOI: 10.1089/rej.2009.0960.Peer-Reviewed Original ResearchConceptsHuman neural stem cellsSubstantia nigraDopamine neuronsParkinson's diseaseFetal dopaminergic neuronsFetal striatal tissueReduction of medicationLittle therapeutic benefitParkinsonian motor deficitsSubsequent clinical trialsDopaminergic neural systemsNonhuman primate brainCell replacement strategiesLong-term improvementStem cellsNeural stem cellsMotor deficitsDopaminergic neuronsNeurological signsCellular repairClinical trialsStriatal targetsStriatal tissueTherapeutic benefitParkinson's patients
2009
Culture System for Rodent and Human Oligodendrocyte Specification, Lineage Progression, and Maturation
Espinosa‐Jeffrey A, Wakeman D, Kim S, Snyder E, de Vellis J. Culture System for Rodent and Human Oligodendrocyte Specification, Lineage Progression, and Maturation. Current Protocols In Stem Cell Biology 2009, 10: 2d.4.1-2d.4.26. PMID: 19725014, DOI: 10.1002/9780470151808.sc02d04s10.Peer-Reviewed Original ResearchLong‐Term Multilayer Adherent Network (MAN) Expansion, Maintenance, and Characterization, Chemical and Genetic Manipulation, and Transplantation of Human Fetal Forebrain Neural Stem Cells
Wakeman DR, Hofmann MR, Redmond DE, Teng YD, Snyder EY. Long‐Term Multilayer Adherent Network (MAN) Expansion, Maintenance, and Characterization, Chemical and Genetic Manipulation, and Transplantation of Human Fetal Forebrain Neural Stem Cells. Current Protocols In Stem Cell Biology 2009, 9: 2d.3.1-2d.3.77. PMID: 19455542, DOI: 10.1002/9780470151808.sc02d03s9.Peer-Reviewed Original ResearchConceptsCentral nervous system disordersNSC/NPCsNeural stem/precursor cellsNeural stem/progenitor cellsNervous system disordersEarly human neurogenesisStem/precursor cellsSmall molecule drug screeningStem/progenitor cellsForebrain neural stem cellsNeural stem cellsHuman neural stem/precursor cellsAdult rodentsTherapeutic modalitiesParkinson's diseaseSystem disordersCadaveric sourcesMonkey brainAlzheimer's diseaseNeurodegenerative disordersHuman neurogenesisNeuronal migrationDiseaseLong-term maintenanceMigratory capability
2007
Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells
Redmond DE, Bjugstad KB, Teng YD, Ourednik V, Ourednik J, Wakeman DR, Parsons XH, Gonzalez R, Blanchard BC, Kim SU, Gu Z, Lipton SA, Markakis EA, Roth RH, Elsworth JD, Sladek JR, Sidman RL, Snyder EY. Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 12175-12180. PMID: 17586681, PMCID: PMC1896134, DOI: 10.1073/pnas.0704091104.Peer-Reviewed Original ResearchConceptsHuman neural stem cellsSubstantia nigraParkinson's diseaseNeural stem cellsTyrosine hydroxylaseBehavioral improvementModel of PDHost substantia nigraStem cellsResponsive progenitor cellsAlpha-synuclein aggregationDA markersNigrostriatal circuitryParkinsonian primatesParkinsonian signsNeuronal numberDA levelsFunctional improvementParkinson modelImmunopositive cellsNormalizing effectDA phenotypeHomeostatic effectsNumber of diseasesProgenitor cells
2006
Adhesive Interactions Between Human Neural Stem Cells and Inflamed Human Vascular Endothelium Are Mediated by Integrins
Mueller F, Serobyan N, Schraufstatter I, DiScipio R, Wakeman D, Loring J, Snyder E, Khaldoyanidi S. Adhesive Interactions Between Human Neural Stem Cells and Inflamed Human Vascular Endothelium Are Mediated by Integrins. Stem Cells 2006, 24: 2367-2372. PMID: 17071855, PMCID: PMC2885956, DOI: 10.1634/stemcells.2005-0568.Peer-Reviewed Original ResearchMeSH KeywordsCell AdhesionCell LineCell MovementEmbryonic Stem CellsEndothelial CellsHumansImmunohistochemistryInflammationIntegrin alpha2Integrin alpha6Integrin beta1IntegrinsNeuronsReverse Transcriptase Polymerase Chain ReactionStress, MechanicalTumor Necrosis Factor-alphaUp-RegulationVascular Cell Adhesion Molecule-1