2024
Multiple intravenous infusions versus a single infusion of mesenchymal stem cells in a rat model of cerebral ischemia.
Yokoyama T, Sasaki M, Nagahama H, Kataoka-Sasaki Y, Ukai R, Oka S, Kocsis J, Honmou O. Multiple intravenous infusions versus a single infusion of mesenchymal stem cells in a rat model of cerebral ischemia. Journal Of Neurosurgery 2024, 1-9. PMID: 39454218, DOI: 10.3171/2024.6.jns241111.Peer-Reviewed Original ResearchInfusion of mesenchymal stem cellsMiddle cerebral artery occlusionMiddle cerebral artery occlusion inductionMesenchymal stem cellsCorpus callosumSystemic infusion of mesenchymal stem cellsMultiple infusionsAcute phaseMesenchymal stem cell infusionCerebral ischemiaStem cellsMultiple intravenous infusionsRat model of cerebral ischemiaHigh-dose infusionPermanent middle cerebral artery occlusionIschemic lesion volumeModels of cerebral ischemiaCC thicknessRandomized clinical trialsCerebral artery occlusionNeural tractsAcute cerebral strokeFunctional recovery outcomesMRI diffusion tensor imagingMSC-3Intravenous Infusion of Autologous Mesenchymal Stem Cells Expanded in Auto Serum for Chronic Spinal Cord Injury Patients: A Case Series
Hirota R, Sasaki M, Iyama S, Kurihara K, Fukushi R, Obara H, Oshigiri T, Morita T, Nakazaki M, Namioka T, Namioka A, Onodera R, Kataoka-Sasaki Y, Oka S, Takemura M, Ukai R, Yokoyama T, Sasaki Y, Yamashita T, Kobayashi M, Okuma Y, Kondo R, Aichi R, Ohmatsu S, Kawashima N, Ito Y, Kobune M, Takada K, Ishiai S, Ogata T, Teramoto A, Yamashita T, Kocsis J, Honmou O. Intravenous Infusion of Autologous Mesenchymal Stem Cells Expanded in Auto Serum for Chronic Spinal Cord Injury Patients: A Case Series. Journal Of Clinical Medicine 2024, 13: 6072. PMID: 39458022, PMCID: PMC11509003, DOI: 10.3390/jcm13206072.Peer-Reviewed Original ResearchAmerican Spinal Injury Association Impairment ScaleSevere spinal cord injuryMesenchymal stem cell infusionAutologous mesenchymal stem cellsIntravenous infusionCase seriesMesenchymal stem cellsQuality of lifeAuto-serumSpinal cord injuryFunctional improvementChronic spinal cord injury patientsIntravenous infusion of mesenchymal stem cellsInfusion of mesenchymal stem cellsStem cellsCord injurySpinal Cord Independence Measure IIIAmerican Spinal Injury Association Impairment Scale grades CSpinal cord injury patientsChronic SCI patientsClassification of Spinal Cord InjuryNeurological Classification of Spinal Cord InjurySignificant functional improvementAssociation Impairment ScaleInternational Standards for Neurological Classification of Spinal Cord InjuryIntravenous infusion of auto-serum-expanded autologous mesenchymal stem cells into chronic severe brain injury patients
Yamaki T, Oka S, Iyama S, Sasaki M, Onodera R, Kataoka-Sasaki Y, Namioka T, Namioka A, Nakazaki M, Takemura M, Ukai R, Yokoyama T, Sasaki Y, Yamashita T, Kobayashi M, Yamaguchi M, Fukino M, Takazawa T, Hayasaka M, Owaku T, Funakura M, Onodera S, Ito Y, Kobune M, Kato J, Ishiai S, Kocsis J, Odaki M, Iwadate Y, Kobayashi S, Honmou O. Intravenous infusion of auto-serum-expanded autologous mesenchymal stem cells into chronic severe brain injury patients. Interdisciplinary Neurosurgery 2024, 36: 101927. DOI: 10.1016/j.inat.2023.101927.Peer-Reviewed Original ResearchSevere brain injury patientsAutologous mesenchymal stem cellsBrain injury patientsIntravenous infusionMesenchymal stem cellsAdverse eventsInjury patientsInfused mesenchymal stem cellsHealth Stroke ScaleSerious adverse eventsFugl-Meyer AssessmentInitial case seriesBrain metabolic activityStem cellsMSC infusionStroke ScaleNeurological deteriorationBarthel IndexCase seriesCNS tumorsNeurological functionFunctional statusFunctional improvementChronic patientsPlacebo effect
2023
Repeated intravenous infusion of mesenchymal stem cells enhances recovery of motor function in a rat model with chronic spinal cord injury
Kurihara K, Sasaki M, Nagahama H, Obara H, Fukushi R, Hirota R, Yoshimoto M, Teramoto A, Kocsis J, Yamashita T, Honmou O. Repeated intravenous infusion of mesenchymal stem cells enhances recovery of motor function in a rat model with chronic spinal cord injury. Brain Research 2023, 1817: 148484. PMID: 37442249, DOI: 10.1016/j.brainres.2023.148484.Peer-Reviewed Original ResearchConceptsSpinal cord injuryInfusion of MSCsChronic spinal cord injuryMesenchymal stem cellsAxonal sproutingCord injuryHD-MSCsIntravenous infusionMotor functionVehicle groupWeek 6Single high-dose infusionInjection of MSCsChronic SCI ratsSingle MSC injectionGreater functional recoveryRat SCI modelSingle intravenous infusionHigh-dose infusionLimited treatment optionsGreater functional improvementSingle high doseHigh disease burdenVivo diffusion tensor imagingEx vivo diffusion tensor imagingTherapeutic efficacy of intravenous infusion of mesenchymal stem cells in rat perinatal brain injury
Terada K, Sasaki M, Nagahama H, Kataoka-Sasaki Y, Oka S, Ukai R, Yokoyama T, Iizuka Y, Sakai T, Fukumura S, Tsugawa T, Kocsis J, Honmou O. Therapeutic efficacy of intravenous infusion of mesenchymal stem cells in rat perinatal brain injury. Pediatric Research 2023, 94: 1921-1928. PMID: 37422495, DOI: 10.1038/s41390-023-02717-9.Peer-Reviewed Original ResearchConceptsPerinatal brain injuryBrain injuryMesenchymal stem cellsIntravenous infusionVehicle groupBrain volumeTherapeutic efficacyInfused mesenchymal stem cellsLeft common carotid arteryHistological analysisNon-ischemic hemispherePostnatal day 7Common carotid arteryEmbryonic day 18Stem cellsHypoxia-ischemiaMSC infusionPreterm infantsGABAergic cellsNeurological functionSignificant complicationsCortical synapsesFunctional improvementCarotid arteryIntravenous administration
2022
Enhanced Network in Corticospinal Tracts after Infused Mesenchymal Stem Cells in Spinal Cord Injury
Hirota R, Sasaki M, Kataoka-Sasaki Y, Oshigiri T, Kurihara K, Fukushi R, Oka S, Ukai R, Yoshimoto M, Kocsis JD, Yamashita T, Honmou O. Enhanced Network in Corticospinal Tracts after Infused Mesenchymal Stem Cells in Spinal Cord Injury. Journal Of Neurotrauma 2022, 39: 1665-1677. PMID: 35611987, PMCID: PMC9734021, DOI: 10.1089/neu.2022.0106.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCorticospinal tractMesenchymal stem cellsCord injurySpinal cordSpontaneous recoveryInfused mesenchymal stem cellsLimited spontaneous recoveryDorsal corticospinal tractLateral corticospinal tractStem cellsCST pathwayCST projectionsSCI inductionMSC infusionAxonal sproutingFunctional recoveryLateral funiculusIntravenous infusionAxonal tracerLesion coreMotor pathwaysFunctional improvementCircuit reorganizationMajor projectionsIntravenous Infusion of Autoserum-Expanded Autologous Mesenchymal Stem Cells in Patients With Chronic Brain Injury: Protocol for a Phase 2 Trial
Oka S, Yamaki T, Sasaki M, Ukai R, Takemura M, Yokoyama T, Kataoka-Sasaki Y, Onodera R, Ito YM, Kobayashi S, Kocsis JD, Iwadate Y, Honmou O. Intravenous Infusion of Autoserum-Expanded Autologous Mesenchymal Stem Cells in Patients With Chronic Brain Injury: Protocol for a Phase 2 Trial. JMIR Research Protocols 2022, 11: e37898. PMID: 35793128, PMCID: PMC9301565, DOI: 10.2196/37898.Peer-Reviewed Original ResearchChronic brain injuryAutologous mesenchymal stem cellsSpinal cord injuryINTERNATIONAL REGISTERED REPORT IDENTIFIERBrain injuryIntravenous infusionRankin Scale gradesCord injuryMesenchymal stem cellsClinical trialsScale gradeTherapeutic efficacyJapan Medical Association CenterSapporo Medical University HospitalInvestigator-initiated clinical trialsModified Rankin Scale gradesOpen-label trialPhase 2 studyPhase 2 trialMedical University HospitalCause of disabilityMotor vehicle accidentsPotential therapeutic efficacyProportion of casesStem cells
2021
Repeated intravenous infusion of mesenchymal stem cells for enhanced functional recovery in a rat model of chronic cerebral ischemia.
Takemura M, Sasaki M, Kataoka-Sasaki Y, Kiyose R, Nagahama H, Oka S, Ukai R, Yokoyama T, Kocsis J, Ueba T, Honmou O. Repeated intravenous infusion of mesenchymal stem cells for enhanced functional recovery in a rat model of chronic cerebral ischemia. Journal Of Neurosurgery 2021, 137: 402-411. PMID: 34861644, DOI: 10.3171/2021.8.jns21687.Peer-Reviewed Original ResearchMiddle cerebral artery occlusionInduction of MCAOCorpus callosumMesenchymal stem cellsChronic phaseMotor functionRat modelWeek 8Vehicle groupInterhemispheric connectionsAdministration of MSCsChronic cerebral ischemia modelNeural connectionsChronic stroke modelCerebral artery occlusionChronic cerebral ischemiaIschemic lesion volumeLong-term disabilityGreater functional improvementCerebral ischemia modelEnhanced functional recoveryAnti-neurofilament antibodiesDiffusion tensorSingle systemic infusionStem cellsPossible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat
Tabata H, Sasaki M, Kataoka-Sasaki Y, Shinkai N, Ichihara K, Masumori N, Kocsis JD, Honmou O. Possible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis/bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat. BMC Urology 2021, 21: 156. PMID: 34774029, PMCID: PMC8590770, DOI: 10.1186/s12894-021-00923-3.Peer-Reviewed Original ResearchConceptsHunner-type ICBladder pain syndromeAnti-inflammatory pathwayMSC groupMesenchymal stem cellsPain syndromeAnimal modelsToll-like receptor 7 agonistTherapeutic efficacyBehavior testsRight external jugular veinFemale Sprague-Dawley ratsGFP-positive mesenchymal stem cellsReceptor 7 agonistChronic pelvic painAnti-inflammatory effectsEfficacious treatment optionExperimental animal modelsSprague-Dawley ratsExternal jugular veinReal-time polymerase chain reactionMRNA expression levelsPositive mesenchymal stem cellsStem cellsHunner lesions
2009
Peripheral glial cell differentiation from neurospheres derived from adipose mesenchymal stem cells
Radtke C, Schmitz B, Spies M, Kocsis J, Vogt P. Peripheral glial cell differentiation from neurospheres derived from adipose mesenchymal stem cells. International Journal Of Developmental Neuroscience 2009, 27: 817-823. PMID: 19699793, DOI: 10.1016/j.ijdevneu.2009.08.006.Peer-Reviewed Original ResearchConceptsMesenchymal stem cellsStem cellsGlial-like cellsAdipose-derived mesenchymal stem cellsGlial cell differentiationPeripheral glial cellsGrowth factorEpidermal growth factorGrowth factor receptorMitogen withdrawalFibroblast growth factorBasic fibroblast growth factorCell differentiationDorsal root ganglion neuronsSchwann cell marker S100P75 nerve growth factor receptorAdipose-derived stem cellsNerve growth factor receptorCellular aggregatesSimultaneous expressionOlfactory Ensheathing CellsAppropriate inductionFactor receptorNeurospheresGlia markersDevelopment of a stroke model in the nonhuman primate and a safety study of IV infusion of human mesenchymal stem cells
Sasaki M, Radtke C, Honmou O, Houkin K, Kocsis J. Development of a stroke model in the nonhuman primate and a safety study of IV infusion of human mesenchymal stem cells. Neuroscience Research 2009, 65: s127. DOI: 10.1016/j.neures.2009.09.613.Peer-Reviewed Original Research
2006
Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia
Liu H, Honmou O, Harada K, Nakamura K, Houkin K, Hamada H, Kocsis J. Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia. Brain 2006, 129: 2734-2745. PMID: 16901914, PMCID: PMC2605397, DOI: 10.1093/brain/awl207.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsApoptosisBrain IschemiaGenetic VectorsHumansImage Processing, Computer-AssistedInfarction, Middle Cerebral ArteryMagnetic Resonance ImagingMaleMesenchymal Stem Cell TransplantationMesenchymal Stem CellsModels, AnimalNeovascularization, PathologicNeuropsychological TestsPlacenta Growth FactorPregnancy ProteinsRatsRats, Sprague-DawleyTransduction, GeneticConceptsMiddle cerebral artery occlusionCerebral ischaemiaMesenchymal stem cellsIntravenous deliveryPermanent middle cerebral artery occlusionHuman MSCsControl sham groupLimb placement testRats 3 hCerebral artery occlusionTreadmill stress testPlacental growth factorIntraluminal vascular occlusionEnzyme-linked immunosorbentNon-neural tissuesHuman mesenchymal stem cellsStem cellsAdult bone marrowArtery occlusionInfarcted hemisphereSham groupFunctional outcomeVascular occlusionFunctional deficitsInfarction size
2005
I.v. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat
Nomura T, Honmou O, Harada K, Houkin K, Hamada H, Kocsis J. I.v. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. Neuroscience 2005, 136: 161-169. PMID: 16229956, PMCID: PMC2605391, DOI: 10.1016/j.neuroscience.2005.06.062.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorMesenchymal stem cell groupBrain-derived neurotrophic factor contributesMiddle cerebral artery occlusionStem cell groupCerebral artery occlusionCerebral ischemia modelMesenchymal stem cellsNeurotrophic factorArtery occlusionCell groupsIschemia modelPermanent middle cerebral artery occlusionRat cerebral ischemia modelHuman mesenchymal stem cellsBrain-derived neurotrophic factor (BDNF) geneStem cellsControl sham groupTreadmill stress testRats 6 hFactor contributesNeurotrophic factor geneIntraluminal vascular occlusionAdult bone marrowCerebral ischemiaIntravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat
Honma T, Honmou O, Iihoshi S, Harada K, Houkin K, Hamada H, Kocsis J. Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. Experimental Neurology 2005, 199: 56-66. PMID: 15967439, PMCID: PMC2605388, DOI: 10.1016/j.expneurol.2005.05.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBehavior, AnimalBrain IschemiaCell CountCells, CulturedDisease Models, AnimalExercise TestGreen Fluorescent ProteinsHumansImmunohistochemistryInfusions, IntravenousMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMaleMaze LearningMesenchymal Stem Cell TransplantationMesenchymal Stem CellsPhosphopyruvate HydrataseRatsRats, Sprague-DawleyTime FactorsConceptsMiddle cerebral artery occlusionIntravenous infusionFunctional outcomeLesion sizeTransient middle cerebral artery occlusionMesenchymal stem cellsCerebral artery occlusionCerebral infarction volumeCerebral ischemia modelSpinal cord injurySubsequent histological examinationPotential therapeutic benefitRats 12 hMorris water mazeBone marrow cellsHuman mesenchymal stem cellsStem cellsHTERT-MSCsArtery occlusionInfarction volumeCerebral ischemiaCord injuryFunctional improvementLesion volumeIschemia model