2021
Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis
Chandran RR, Xie Y, Gallardo-Vara E, Adams T, Garcia-Milian R, Kabir I, Sheikh AQ, Kaminski N, Martin KA, Herzog EL, Greif DM. Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis. Nature Communications 2021, 12: 7179. PMID: 34893592, PMCID: PMC8664937, DOI: 10.1038/s41467-021-27499-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationDisease Models, AnimalDown-RegulationExtracellular MatrixFemaleFibroblastsFibrosisHumansKruppel-Like Factor 4LungLung InjuryMaleMesenchymal Stem CellsMiceMice, Inbred C57BLMyofibroblastsReceptor, Platelet-Derived Growth Factor betaRespiratory Tract DiseasesSignal TransductionTransforming Growth Factor betaConceptsMesenchymal cell typesPlatelet-derived growth factor receptorSmooth muscle actinLung fibrosisKruppel-like factor 4Forkhead box M1Growth factor receptorCell transitionCell typesExtracellular matrixDistinct rolesKLF4Box M1C chemokine ligandMesenchymal cell subtypesFactor receptorPro-fibrotic effectsFactor 4PDGFRMesenchymeCellsMacrophage accumulationKLF4 levelsChemokine ligandLung fibrogenesis
2017
Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model
Huleihel L, Sellares J, Cardenes N, Álvarez D, Faner R, Sakamoto K, Yu G, Kapetanaki MG, Kaminski N, Rojas M. Modified mesenchymal stem cells using miRNA transduction alter lung injury in a bleomycin model. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2017, 313: l92-l103. PMID: 28385811, PMCID: PMC5538868, DOI: 10.1152/ajplung.00323.2016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersBleomycinBone Marrow CellsCollagenCytokinesDisease Models, AnimalFemaleGene Expression RegulationGene Regulatory NetworksHumansInterleukin-6Leukocyte Common AntigensLung InjuryMesenchymal Stem Cell TransplantationMesenchymal Stem CellsMice, Inbred C57BLMicroRNAsRNA, MessengerSurvival AnalysisTransduction, GeneticTransfectionWeight LossConceptsBone marrow-derived mesenchymal stem cellsMesenchymal stem cellsLung fibrosisLate administrationBleomycin modelMiR-154Different preclinical modelsStem cellsCD45-positive cellsMurine bleomycin modelMarrow-derived mesenchymal stem cellsInitial weight lossLower survival rateAshcroft scoreLung injuryBleomycin instillationFibrotic changesCytokine expressionMice groupsLung tissueOH-prolinePreclinical modelsProtective effectTreatment groupsSurvival rateLoss of Twist1 in the Mesenchymal Compartment Promotes Increased Fibrosis in Experimental Lung Injury by Enhanced Expression of CXCL12
Tan J, Tedrow JR, Nouraie M, Dutta JA, Miller DT, Li X, Yu S, Chu Y, Juan-Guardela B, Kaminski N, Ramani K, Biswas PS, Zhang Y, Kass DJ. Loss of Twist1 in the Mesenchymal Compartment Promotes Increased Fibrosis in Experimental Lung Injury by Enhanced Expression of CXCL12. The Journal Of Immunology 2017, 198: 2269-2285. PMID: 28179498, PMCID: PMC5337810, DOI: 10.4049/jimmunol.1600610.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisIPF patientsLung injuryPulmonary fibrosisT cellsFibrotic lung injuryIPF lung fibroblastsExperimental lung injuryT-cell pathwayApoptosis-resistant fibroblastsMatrix-producing cellsChemoattractant CXCL12Exaggerated fibrosisIPF phenotypeCollagen-producing cellsTranscription factor Twist1Prosurvival phenotypeFibrosisTwist1 expressionIncreased expressionLung fibroblastsCXCL12Low expressionHigh expressionCell pathways
2015
Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs
Phinney DG, Di Giuseppe M, Njah J, Sala E, Shiva S, St Croix CM, Stolz DB, Watkins SC, Di YP, Leikauf GD, Kolls J, Riches DW, Deiuliis G, Kaminski N, Boregowda SV, McKenna DH, Ortiz LA. Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nature Communications 2015, 6: 8472. PMID: 26442449, PMCID: PMC4598952, DOI: 10.1038/ncomms9472.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArrestinsBlotting, WesternCell-Derived MicroparticlesExosomesExtracellular VesiclesFlow CytometryHumansMacrophagesMesenchymal Stem CellsMiceMicroRNAsMicroscopy, ElectronMitochondriaMitophagyMyeloid Differentiation Factor 88Oxidative StressReceptors, ImmunologicSignal TransductionSilicosisToll-Like Receptor 4Toll-Like Receptor 9Toll-Like ReceptorsConceptsMesenchymal stem cellsStem cellsDomain-containing protein 1Stem cell nicheHealthy mitochondrial functionHaematopoietic stem cellsCell nichePlasma membraneToll-like receptor signalingIntracellular oxidative stressMitochondrial functionExtracellular vesiclesMicro RNAsReceptor signalingProtein 1MitophagyMSC survivalMitochondriaOxidative stressMacrophage functionVesiclesCellsRecent studiesMacrophage activationMacrophages
2014
Aging Mesenchymal Stem Cells Fail to Protect Because of Impaired Migration and Antiinflammatory Response
Bustos ML, Huleihel L, Kapetanaki MG, Lino-Cardenas CL, Mroz L, Ellis BM, McVerry BJ, Richards TJ, Kaminski N, Cerdenes N, Mora AL, Rojas M. Aging Mesenchymal Stem Cells Fail to Protect Because of Impaired Migration and Antiinflammatory Response. American Journal Of Respiratory And Critical Care Medicine 2014, 189: 787-798. PMID: 24559482, PMCID: PMC4061541, DOI: 10.1164/rccm.201306-1043oc.Peer-Reviewed Original ResearchConceptsBone marrow-derived MSCsMesenchymal stem cellsChemokine receptorsAcute lung injuryAcute lung diseaseSite of injuryAge-dependent decreaseBone marrow-derived mesenchymal stem cellsMarrow-derived mesenchymal stem cellsInflammatory response genesSuch age-related changesAge-related phenomenonStem cellsAge-related changesAdoptive transferLung injuryEndotoxemic miceLung diseaseAntiinflammatory responseFunctional impairmentMore inflammationProtective effectOld miceParacrine mechanismsAlveolar epithelium
2013
Activation of Human Mesenchymal Stem Cells Impacts Their Therapeutic Abilities in Lung Injury by Increasing Interleukin (IL)-10 and IL-1RN Levels
Bustos ML, Huleihel L, Meyer EM, Donnenberg AD, Donnenberg VS, Sciurba JD, Mroz L, McVerry BJ, Ellis BM, Kaminski N, Rojas M. Activation of Human Mesenchymal Stem Cells Impacts Their Therapeutic Abilities in Lung Injury by Increasing Interleukin (IL)-10 and IL-1RN Levels. Stem Cells Translational Medicine 2013, 2: 884-895. PMID: 24089414, PMCID: PMC3808203, DOI: 10.5966/sctm.2013-0033.Peer-Reviewed Original ResearchConceptsAcute respiratory distress syndromeAnti-inflammatory effectsBone marrow aspirateReceptor antagonistMarrow aspiratesMesenchymal stem cellsBronchoalveolar lavage inflammatory cellsIL-1 receptor antagonistHuman mesenchymal stem cellsLung injury scoreRespiratory distress syndromeAnti-inflammatory capacityExpression of interleukinStem cellsARDS patientsLung inflammationLung injuryDistress syndromeEndotoxemic micePulmonary edemaInflammatory cellsInjury scoreClinical trialsEffective therapyImmunomodulatory phenotype