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 cellsDiseaseA Biomarker for Predicting Responsiveness to Stem Cell Therapy Based on Mechanism-of-Action: Evidence from Cerebral Injury
Hartman R, Nathan N, Ghosh N, Pernia C, Law J, Nuryyev R, Plaia A, Yusof A, Tone B, Dulcich M, Wakeman D, Dilmac N, Niles W, Sidman R, Obenaus A, Snyder E, Ashwal S. A Biomarker for Predicting Responsiveness to Stem Cell Therapy Based on Mechanism-of-Action: Evidence from Cerebral Injury. Cell Reports 2020, 31: 107622. PMID: 32402283, DOI: 10.1016/j.celrep.2020.107622.Peer-Reviewed Original ResearchConceptsHuman neural stem cellsHypoxic-ischemic injuryTherapeutic mechanismCerebral hypoxic-ischemic injuryCell therapyMolecular profileHierarchical region splittingStem cell therapyNeural stem cellsCerebral injurySelection biomarkerPredicting ResponsivenessNecrotic coreCognitive outcomesBiomarkersTherapyInjuryLesionsStem cellsResponsivenessPenumbraCellsCore volumeSalvageabilityRecipients
2017
Cell Replacement Strategies for Parkinson’s Disease
Chatterjee D, Wakeman D, Kordower J. Cell Replacement Strategies for Parkinson’s Disease. Molecular And Translational Medicine 2017, 73-83. DOI: 10.1007/978-3-319-57153-9_4.Peer-Reviewed Original ResearchCell replacement strategiesFetal graftsClinical trialsParkinson's diseaseAnimal modelsDouble-blind clinical assessmentOpen-label clinical trialCareful subject selectionDopamine cell replacementGraft-induced dyskinesiaPotential clinical efficacyProgressive neurodegenerative disorderCell transplantation therapyPrion-like transmissionStem cellsGraft microenvironmentMotor dysfunctionMotor symptomsNigrostriatal pathwayClinical efficacyReplacement therapyDopaminergic neuronsLewy bodiesSpecific therapyCell replacement therapy
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 depolarizationHoming 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
2010
Cellular 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
Functional Multipotency of Neural Stem Cells and Its Therapeutic Implications
Teng Y, Kabatas S, Li J, Wakeman D, Snyder E, Sidman R. Functional Multipotency of Neural Stem Cells and Its Therapeutic Implications. 2009, 255-270. DOI: 10.1007/978-90-481-3375-8_16.Peer-Reviewed Original Research
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