2021
SLIT2/ROBO signaling in tumor-associated microglia/macrophages drives glioblastoma immunosuppression and vascular dysmorphia
Geraldo LH, Xu Y, Jacob L, Pibouin-Fragner L, Rao R, Maïssa N, Verreault M, Lemaire N, Knosp C, Lesaffre C, Daubon T, Dejaegher J, Solie L, Rudewicz J, Viel T, Tavitian B, De Vleeschouwer S, Sanson M, Bikfalvi A, Idbaih A, Lu QR, Lima F, Thomas. JL, Eichmann A, Mathivet T. SLIT2/ROBO signaling in tumor-associated microglia/macrophages drives glioblastoma immunosuppression and vascular dysmorphia. Journal Of Clinical Investigation 2021, 131 PMID: 34181595, PMCID: PMC8363292, DOI: 10.1172/jci141083.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsDisease ProgressionGene Expression Regulation, NeoplasticGene Knockdown TechniquesGlioblastomaHeterograftsHumansImmune ToleranceIntercellular Signaling Peptides and ProteinsMacrophagesMiceMice, Inbred C57BLMicrogliaNerve Tissue ProteinsPrognosisReceptors, ImmunologicSignal TransductionTumor MicroenvironmentConceptsSLIT2/ROBOTumor growthPatient-derived GBM xenograftsTumor microenvironmentKnockdown of SLIT2Tumor vessel functionMouse glioma cellsImmunotherapeutic targetPoor survivalGBM xenograftsBrain tumorsGBM microenvironmentMacrophage invasionSLIT2 expressionMalignant progressionVessel functionMacrophage chemotaxisGlioma cellsEnhanced efficacySLIT2Migration of cellsImmunosuppressionImmunotherapyGene expression profilesRoundabout 1
2020
VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours
Song E, Mao T, Dong H, Boisserand LSB, Antila S, Bosenberg M, Alitalo K, Thomas JL, Iwasaki A. VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours. Nature 2020, 577: 689-694. PMID: 31942068, PMCID: PMC7100608, DOI: 10.1038/s41586-019-1912-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsCD8-Positive T-LymphocytesCell Cycle CheckpointsCell Line, TumorCell MovementCentral Nervous SystemCross-PrimingFemaleGlioblastomaHEK293 CellsHumansImmunologic MemoryImmunologic SurveillanceLymph NodesLymphangiogenesisLymphatic VesselsMaleMelanomaMeningesMiceMice, Inbred C57BLProgrammed Cell Death 1 ReceptorVascular Endothelial Growth Factor CConceptsCD8 T cellsCentral nervous systemT cellsImmune responseBrain tumorsImmune surveillanceLymphatic drainageNervous systemAntigen-specific immune responsesDeep cervical lymph nodesCapacity of VEGFCervical lymph nodesCheckpoint blockade therapyMeningeal lymphatic systemVascular endothelial growth factor CNew therapeutic approachesUncontrolled tumor growthMeningeal lymphatic vasculatureBlockade therapyLymph nodesTherapeutic approachesMouse modelTumor growthMemory responsesTumors
2019
Minimally Invasive Delivery of Microbeads with Encapsulated, Viable and Quiescent Neural Stem Cells to the Adult Subventricular Zone
Matta R, Lee S, Genet N, Hirschi KK, Thomas JL, Gonzalez AL. Minimally Invasive Delivery of Microbeads with Encapsulated, Viable and Quiescent Neural Stem Cells to the Adult Subventricular Zone. Scientific Reports 2019, 9: 17798. PMID: 31780709, PMCID: PMC6882840, DOI: 10.1038/s41598-019-54167-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell EncapsulationCell LineCell ProliferationCell SurvivalEndothelial CellsLateral VentriclesMaleMatrix MetalloproteinasesMiceMice, Inbred C57BLMicrospheresNeural Stem CellsNeuronsPolyethylene GlycolsRecovery of FunctionStem Cell NicheStem Cell TransplantationConceptsEndothelial cellsSubventricular zoneNSC quiescenceNon-injury modelQuiescent neural stem cellsAdult subventricular zoneNeuronal stem cellsStem cellsNeural stem cellsFunctional recoveryNeurological injuryInflammatory responseNeural stem cell maintenanceNSC deliveryNeural tissue repairNeurological diseasesMouse brainCell therapyNSC viabilityBrainTissue repairInjuryCo-encapsulated cellsSurvivalDeliveryAnatomy and function of the vertebral column lymphatic network in mice
Jacob L, Boisserand LSB, Geraldo LHM, de Brito Neto J, Mathivet T, Antila S, Barka B, Xu Y, Thomas JM, Pestel J, Aigrot MS, Song E, Nurmi H, Lee S, Alitalo K, Renier N, Eichmann A, Thomas JL. Anatomy and function of the vertebral column lymphatic network in mice. Nature Communications 2019, 10: 4594. PMID: 31597914, PMCID: PMC6785564, DOI: 10.1038/s41467-019-12568-w.Peer-Reviewed Original ResearchConceptsLymphatic vesselsCentral nervous system immune responseFocal spinal cord lesionsT cell infiltrationSpinal cord lesionsSpinal cord injuryCNS immunityCord lesionsMeningeal lymphatic vesselsSympathetic gangliaCord injuryCell infiltrationSpinal cordInflammatory responseEpidural spaceThoracic ductImmune responseDura materSpinal tissuePotential targetVertebral tissuesLymphatic networkSpine segmentsTraditional histologyLittle information
2017
Development and plasticity of meningeal lymphatic vessels
Antila S, Karaman S, Nurmi H, Airavaara M, Voutilainen MH, Mathivet T, Chilov D, Li Z, Koppinen T, Park JH, Fang S, Aspelund A, Saarma M, Eichmann A, Thomas JL, Alitalo K. Development and plasticity of meningeal lymphatic vessels. Journal Of Experimental Medicine 2017, 214: 3645-3667. PMID: 29141865, PMCID: PMC5716035, DOI: 10.1084/jem.20170391.Peer-Reviewed Original ResearchAnimalsAnimals, NewbornBiological TransportCerebrospinal FluidDependovirusGene DeletionHumansIndolesInjections, IntraventricularLymph NodesLymphangiogenesisLymphatic VesselsMaleMeningesMice, Inbred C57BLMicrospheresMyocytes, Smooth MuscleProtein Kinase InhibitorsPyrrolesSignal TransductionSpinal CordSunitinibVascular Endothelial Growth Factor CVascular Endothelial Growth Factor DVascular Endothelial Growth Factor Receptor-3Modulation of Endothelial Bone Morphogenetic Protein Receptor Type 2 Activity by Vascular Endothelial Growth Factor Receptor 3 in Pulmonary Arterial Hypertension
Hwangbo C, Lee HW, Kang H, Ju H, Wiley DS, Papangeli I, Han J, Kim JD, Dunworth WP, Hu X, Lee S, El-Hely O, Sofer A, Pak B, Peterson L, Comhair S, Hwang EM, Park JY, Thomas J, Bautch VL, Erzurum SC, Chun HJ, Jin SW. Modulation of Endothelial Bone Morphogenetic Protein Receptor Type 2 Activity by Vascular Endothelial Growth Factor Receptor 3 in Pulmonary Arterial Hypertension. Circulation 2017, 135: 2288-2298. PMID: 28356442, PMCID: PMC5523010, DOI: 10.1161/circulationaha.116.025390.Peer-Reviewed Original ResearchConceptsBMP receptor type 2Vascular endothelial growth factor receptor 3Growth factor receptor 3Zebrafish embryosPulmonary arterial endothelial cellsArterial endothelial cellsVEGFR3 expressionBone morphogenetic protein (BMP) signalingPulmonary arterial hypertensionMorphogenetic protein signalingEndothelial cellsFamilial pulmonary arterial hypertensionBMPR2 functionsPrimary lung endothelial cellsImpaired BMPBMP signalingBMP stimulationProtein signalingReceptor 3Endothelial-specific deletionEctopic angiogenesisKey regulatorHuman endothelial cellsArterial hypertensionLung endothelial cells
2016
Increased Nanoparticle Delivery to Brain Tumors by Autocatalytic Priming for Improved Treatment and Imaging
Han L, Kong DK, Zheng MQ, Murikinati S, Ma C, Yuan P, Li L, Tian D, Cai Q, Ye C, Holden D, Park JH, Gao X, Thomas JL, Grutzendler J, Carson RE, Huang Y, Piepmeier JM, Zhou J. Increased Nanoparticle Delivery to Brain Tumors by Autocatalytic Priming for Improved Treatment and Imaging. ACS Nano 2016, 10: 4209-4218. PMID: 26967254, PMCID: PMC5257033, DOI: 10.1021/acsnano.5b07573.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBiological TransportBlood-Brain BarrierBrain NeoplasmsCell Line, TumorDecanoic AcidsDrug Delivery SystemsEthanolaminesFemaleGenetic TherapyHeterograftsHumansMatrix Metalloproteinase 2MiceMice, Inbred C57BLNanoparticlesOptical ImagingPaclitaxelPermeabilityPolymersPurinesPyrazolesScorpion VenomsTranscytosisTumor MicroenvironmentConceptsBlood-brain barrierLow delivery efficiencyTransport of nanoparticlesCancer gene therapyNanoparticle deliveryMore nanoparticlesBrain tumorsNanoparticlesDelivery efficiencyGene therapySystemic deliveryNPsBrain malignanciesBBB modulatorsPharmacological agentsBrain cancerBrain regionsTumorsDeliveryBrainImproved treatmentInadequate amountsPositive feedback loopChemotherapyMalignancy
2015
Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis
Poulos MG, Crowley MJP, Gutkin MC, Ramalingam P, Schachterle W, Thomas JL, Elemento O, Butler JM. Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis. Stem Cell Reports 2015, 5: 881-894. PMID: 26441307, PMCID: PMC4649106, DOI: 10.1016/j.stemcr.2015.08.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytokinesEndothelial Progenitor CellsHematopoiesisMiceMice, Inbred C57BLProto-Oncogene Proteins c-aktStem Cell NicheStromal CellsConceptsBM endothelial cellsHematopoietic stem cellsBone marrowDevelopment of therapiesAdult bone marrowCytokine profileMyeloablative regimensMyeloablative irradiationStem cell factorRegenerative hematopoiesisPerivascular cellsCellular therapyEndothelial cellsDisease statesCytokine supplementationVascular platformCell factorVascular nicheTherapyPrevious reportsStem cellsVascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans
Han J, Calvo CF, Kang TH, Baker KL, Park JH, Parras C, Levittas M, Birba U, Pibouin-Fragner L, Fragner P, Bilguvar K, Duman RS, Nurmi H, Alitalo K, Eichmann AC, Thomas JL. Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans. Cell Reports 2015, 10: 1158-1172. PMID: 25704818, PMCID: PMC4685253, DOI: 10.1016/j.celrep.2015.01.049.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell ProliferationCells, CulturedEmbryonic Stem CellsExtracellular Signal-Regulated MAP KinasesHippocampusHumansMiceMice, Inbred C57BLNeural Stem CellsNeurogenesisProto-Oncogene Proteins c-aktRecombinant ProteinsSignal TransductionVascular Endothelial Growth Factor CVascular Endothelial Growth Factor Receptor-3ConceptsHuman embryonic stem cellsNeural stem cellsVascular endothelial growth factor receptor 3Growth factor receptor 3NSC activationStem cellsProgenitor cellsAdult hippocampal neural stem cellsEmbryonic stem cellsNeural stem cell activationStem cell activationQuiescent neural stem cellsNeural progenitor cellsCell fateReceptor 3Specific regulatorsAdult mammalian hippocampusMolecular mechanismsCell cycleHippocampal neural stem cellsLigand VEGFERK pathwayConditional deletionNew neuronsVEGFR3
2014
Neural-Specific Deletion of Htra2 Causes Cerebellar Neurodegeneration and Defective Processing of Mitochondrial OPA1
Patterson VL, Zullo AJ, Koenig C, Stoessel S, Jo H, Liu X, Han J, Choi M, DeWan AT, Thomas JL, Kuan CY, Hoh J. Neural-Specific Deletion of Htra2 Causes Cerebellar Neurodegeneration and Defective Processing of Mitochondrial OPA1. PLOS ONE 2014, 9: e115789. PMID: 25531304, PMCID: PMC4274161, DOI: 10.1371/journal.pone.0115789.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBehavior, AnimalBlotting, WesternCell ProliferationCerebellumFemaleGTP PhosphohydrolasesHigh-Temperature Requirement A Serine Peptidase 2MaleMiceMice, Inbred C57BLMice, KnockoutMitochondriaMitochondrial ProteinsNerve DegenerationNeuronsParkinson DiseaseReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSequence DeletionSerine EndopeptidasesSignal TransductionConceptsNeural-specific deletionStriatal neuronal lossPostnatal day 18Days of ageNeuronal lossNeurological symptomsParkinson's diseaseMouse modelParkinsonian phenotypeSystemic effectsMitochondrial Opa1Day 18Premature deathMutant miceNeural contributionsMiceCerebellar neurodegenerationKey moleculesStructural anomaliesAbnormal activityAbnormal morphologyCerebellumDiseaseComplete penetranceDeath
2010
Nitric Oxide Plays a Key Role in Myelination in the Developing Brain
Olivier P, Loron G, Fontaine R, Pansiot J, Dalous J, Thi H, Charriaut-Marlangue C, Thomas J, Mercier J, Gressens P, Baud O. Nitric Oxide Plays a Key Role in Myelination in the Developing Brain. Journal Of Neuropathology & Experimental Neurology 2010, 69: 828-837. PMID: 20613635, DOI: 10.1097/nen.0b013e3181ea5203.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, InhalationAge FactorsAnimalsAnimals, NewbornAntigensBehavioral SymptomsBrainCell ProliferationCentral Nervous SystemDose-Response Relationship, DrugEnzyme InhibitorsExploratory BehaviorFemaleFree Radical ScavengersGene Expression Regulation, DevelopmentalIn Situ Nick-End LabelingKi-67 AntigenMaleMiceMice, Inbred C57BLMyelin Basic ProteinMyelin Proteolipid ProteinNerve Fibers, MyelinatedNerve Tissue ProteinsNeuronsNeuropsychological TestsNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide Synthase Type IIO AntigensOligodendrogliaProteoglycansRatsRats, Sprague-DawleySpace PerceptionSpatial BehaviorStatistics, NonparametricConceptsEndogenous NONitric oxide synthase inhibitor N-nitro-L-arginine methyl esterN-nitro-L-arginine methyl esterL-NAME-treated animalsNitric oxidePerinatal brain damageSubsequent behavioral deficitsCentral nervous system myelinationNeonatal exposureC57BL/6 miceNeonatal periodBrain damagePromising therapyBehavioral deficitsMouse pupsImmature oligodendrocytesPotential new avenuesWhite matterLow dosesProliferative effectMyelination defectsMyelinationTransient increaseINODeleterious effectsNeuropilin-2 mediates VEGF-C–induced lymphatic sprouting together with VEGFR3
Xu Y, Yuan L, Mak J, Pardanaud L, Caunt M, Kasman I, Larrivée B, del Toro R, Suchting S, Medvinsky A, Silva J, Yang J, Thomas JL, Koch AW, Alitalo K, Eichmann A, Bagri A. Neuropilin-2 mediates VEGF-C–induced lymphatic sprouting together with VEGFR3. Journal Of Cell Biology 2010, 188: 115-130. PMID: 20065093, PMCID: PMC2812843, DOI: 10.1083/jcb.200903137.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ShapeCells, CulturedEndothelial CellsFemaleLymphangiogenesisLymphatic VesselsMaleMiceMice, Inbred C57BLMice, Inbred StrainsMice, TransgenicNeuropilin-2Protein BindingVascular Endothelial Growth Factor CVascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3ConceptsLymphatic vessel sproutingVEGF receptor 2Lymphangiogenic vascular endothelial growth factors CSprouting defectsNeuropilin-2Vessel sproutingVascular endothelial growth factor CVEGF-C bindingAntibody treatmentEndothelial tip cellsReceptor 2Lymph vesselsLymphatic sproutingGenetic deletionHeterozygous miceTransmembrane receptorsTip cellsAdult organsMiceCell extensionsNRP2Vascular systemVascular sprout formationVascular sproutingVEGF
2008
Early Neuronal and Glial Fate Restriction of Embryonic Neural Stem Cells
Delaunay D, Heydon K, Cumano A, Schwab M, Thomas J, Suter U, Nave K, Zalc B, Spassky N. Early Neuronal and Glial Fate Restriction of Embryonic Neural Stem Cells. Journal Of Neuroscience 2008, 28: 2551-2562. PMID: 18322099, PMCID: PMC6671176, DOI: 10.1523/jneurosci.5497-07.2008.Peer-Reviewed Original ResearchConceptsGlial cellsEmbryonic neural stem cellsNeuronal progenitor cellsFate restrictionRadial glial cellsEmbryonic developmentNeural stem cellsNeuroepithelial progenitorsFate mappingNeuronal precursorsNeuroepithelial cellsNeurogenic periodStem cellsClonal analysisGlial precursorsProgenitor cellsGliogenic periodCellsProteolipid proteinNew poolDifferent time pointsLater stagesEmbryogenesis
2004
Evaluation of Hematopoietic Potential Generated by Transplantation of Muscle-Derived Stem Cells in Mice
Farace F, Prestoz L, Badaoui S, Guillier M, Haond C, Opolon P, Thomas JL, Zalc B, Vainchenker W, Turhan AG. Evaluation of Hematopoietic Potential Generated by Transplantation of Muscle-Derived Stem Cells in Mice. Stem Cells And Development 2004, 13: 83-92. PMID: 15068696, DOI: 10.1089/154732804773099281.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesBone Marrow CellsBone Marrow TransplantationCell DivisionCell LineageCell SeparationCell TransplantationChimeraFemaleFlow CytometryHematopoiesisHematopoietic Stem CellsHematopoietic SystemIn Situ Hybridization, FluorescenceKiller Cells, NaturalLeukocyte Common AntigensMaleMiceMice, Inbred C57BLMusclesPolymerase Chain ReactionSex FactorsStem CellsT-LymphocytesConceptsMarrow transplantationUse of muscleStem cellsTransplantation of musclesNatural killer cellsMarrow-derived stem cellsMuscle-derived hematopoietic stem cellsLevel of CFUMuscle-derived stem cellsMarrow stem cellsMuscle tissueMuscle transplantsKiller cellsTertiary recipientsHematopoietic chimerismMuscle graftsIrradiated miceAdult miceTransplantationHematopoietic stem cellsSecondary recipientsSimilar potencyMiceMurine muscleSerial transplantation