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SARS-CoV-2 leverages airway epithelial protective mechanism for viral infection
Greaney A, Raredon M, Kochugaeva M, Niklason L, Levchenko A. SARS-CoV-2 leverages airway epithelial protective mechanism for viral infection. IScience 2023, 26: 106175. PMID: 36788793, PMCID: PMC9912025, DOI: 10.1016/j.isci.2023.106175.Peer-Reviewed Original ResearchSingle-cell RNA sequencing datasetsCell-cell communicationRNA sequencing datasetsViral infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infectionEarly SARS-CoV-2 infectionSequencing datasetsSARS-CoV-2 infectionRepair mechanismsEarly viral entryTissue repair mechanismsMature ciliated cellsAlternative therapeutic approachSARS-CoV-2 virusResponse mechanismsFeedforward loopCell precursorsRapid differentiationViral entryBronchial epitheliumTherapeutic approachesBarrier tissuesKey mechanismCiliated cellsInfectionDecellularization compromises mechanical and structural properties of the native trachea
Greaney A, Ramachandra A, Yuan Y, Korneva A, Humphrey J, Niklason L. Decellularization compromises mechanical and structural properties of the native trachea. Biomaterials And Biosystems 2023, 9: 100074. PMID: 36967724, PMCID: PMC10036236, DOI: 10.1016/j.bbiosy.2023.100074.Peer-Reviewed Original ResearchMechanical behaviorGraft failureNative tracheaMechanical failureTissue engineering technologyDepletion of proteoglycansAirway narrowingAirway replacementClinical interventionsWestern blotTracheaMajor causeTracheal graftsEngineering technologyHistological stainingTracheal replacementDifferent decellularization protocolsSignificant differencesClinical implantationTissue repairCollagen IStructural deteriorationStructural propertiesDecellularization protocolGreat potentialThe History of Engineered Tracheal Replacements: Interpreting the Past and Guiding the Future
Greaney A, Niklason L. The History of Engineered Tracheal Replacements: Interpreting the Past and Guiding the Future. Tissue Engineering Part B Reviews 2020, 27: 341-352. PMID: 33045942, PMCID: PMC8390779, DOI: 10.1089/ten.teb.2020.0238.Peer-Reviewed Original ResearchConceptsFailure modesTracheal graftsTracheal replacementGraft mechanicsDesign criteriaInert materialLong segment defectType of graftRecent preclinical workClinical care prioritiesRigid tubeLeuven protocolTracheal allograftsClinical followAirway reconstructionCadaveric allograftsCircumferential defectsTissue analysis techniquesEngineersPreclinical workReplacement graftsCare prioritiesGraft performanceHuman patientsGraftPlatform Effects on Regeneration by Pulmonary Basal Cells as Evaluated by Single-Cell RNA Sequencing
Greaney AM, Adams TS, Raredon M, Gubbins E, Schupp JC, Engler AJ, Ghaedi M, Yuan Y, Kaminski N, Niklason LE. Platform Effects on Regeneration by Pulmonary Basal Cells as Evaluated by Single-Cell RNA Sequencing. Cell Reports 2020, 30: 4250-4265.e6. PMID: 32209482, PMCID: PMC7175071, DOI: 10.1016/j.celrep.2020.03.004.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingBasal marker expressionBasal cellsChronic pulmonary diseaseRat tracheal epitheliumPulmonary diseaseRNA sequencingCell-based therapiesRat tracheaAir-liquid interfaceTissue graftMarker expressionTracheal epitheliumRegenerative outcomesTracheaEpithelial progenitorsDifferential outcomesEpitheliumOutcomesWhole organPopulation level
2023
Rational engineering of lung alveolar epithelium
Leiby K, Yuan Y, Ng R, Raredon M, Adams T, Baevova P, Greaney A, Hirschi K, Campbell S, Kaminski N, Herzog E, Niklason L. Rational engineering of lung alveolar epithelium. Npj Regenerative Medicine 2023, 8: 22. PMID: 37117221, PMCID: PMC10147714, DOI: 10.1038/s41536-023-00295-2.Peer-Reviewed Original Research
2022
Computation and visualization of cell–cell signaling topologies in single-cell systems data using Connectome
Raredon MSB, Yang J, Garritano J, Wang M, Kushnir D, Schupp JC, Adams TS, Greaney AM, Leiby KL, Kaminski N, Kluger Y, Levchenko A, Niklason LE. Computation and visualization of cell–cell signaling topologies in single-cell systems data using Connectome. Scientific Reports 2022, 12: 4187. PMID: 35264704, PMCID: PMC8906120, DOI: 10.1038/s41598-022-07959-x.Peer-Reviewed Original ResearchExpression of the transcription factor PU.1 induces the generation of microglia-like cells in human cortical organoids
Cakir B, Tanaka Y, Kiral FR, Xiang Y, Dagliyan O, Wang J, Lee M, Greaney AM, Yang WS, duBoulay C, Kural MH, Patterson B, Zhong M, Kim J, Bai Y, Min W, Niklason LE, Patra P, Park IH. Expression of the transcription factor PU.1 induces the generation of microglia-like cells in human cortical organoids. Nature Communications 2022, 13: 430. PMID: 35058453, PMCID: PMC8776770, DOI: 10.1038/s41467-022-28043-y.Peer-Reviewed Original ResearchConceptsHuman embryonic stem cellsHuman cortical organoidsTranscription factor PUSingle-cell RNA sequencingMicroglia-like cellsSingle-cell transcriptomicsEmbryonic stem cellsDisease stage IIIRole of microgliaAD-associated genesExpression of genesCortical organoidsNeurodegenerative disordersRNA sequencingMolecular damageIntact complementStem cellsDysfunction of microgliaFunctional microgliaReduced expressionGenesCell clustersExpressionChemokine systemHuman microglia
2021
Pressure-Regulated Ventilator Splitting for Disaster Relief: Design, Testing, and Clinical Experience
Raredon MSB, Fisher C, Heerdt PM, Schonberger RB, Nargi A, Nivison S, Fajardo E, Deshpande R, Akhtar S, Greaney AM, Belter J, Raredon T, Zinter J, McKee A, Michalski M, Baevova P, Niklason LE. Pressure-Regulated Ventilator Splitting for Disaster Relief: Design, Testing, and Clinical Experience. Anesthesia & Analgesia 2021, 134: 1094-1105. PMID: 34928890, DOI: 10.1213/ane.0000000000005825.Peer-Reviewed Original ResearchConceptsPositive end-expiratory pressureClinical experienceIndividualized positive end-expiratory pressureIntensive care unitEnd-expiratory pressureCoronavirus disease 2019 (COVID-19) pandemicHealth care teamDisease 2019 pandemicVentilatory supportIll patientsCare unitCare teamVentilator sharingFuture clinical applicationsPatientsIndependent careVentilator capacityClinical applicationCOVID-19 pandemicVentilatorClinical environmentOutline recommendationsMass traumaPandemicHospitalA Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds
Yuan Y, Leiby KL, Greaney AM, Raredon MSB, Qian H, Schupp JC, Engler AJ, Baevova P, Adams TS, Kural MH, Wang J, Obata T, Yoder MC, Kaminski N, Niklason LE. A Pulmonary Vascular Model From Endothelialized Whole Organ Scaffolds. Frontiers In Bioengineering And Biotechnology 2021, 9: 760309. PMID: 34869270, PMCID: PMC8640093, DOI: 10.3389/fbioe.2021.760309.Peer-Reviewed Original ResearchVascular diseaseEndothelial phenotypeLung vascular diseaseAcute lung injuryPulmonary microvascular functionWhole lung scaffoldsVascular barrier functionLung injuryMicrovascular functionEndothelial cell coverageSingle-cell RNA-sequencing analysisLPS treatmentProinflammatory signalsWhole lungLung endotheliumLung systemVascular barrierOrgan engineering approachesBarrier functionLungWhole-organ scaffoldsVascular structuresDrug mechanismsEndotheliumDiseaseMicrovascular fluid flow in ex vivo and engineered lungs
Raredon MSB, Engler AJ, Yuan Y, Greaney AM, Niklason LE. Microvascular fluid flow in ex vivo and engineered lungs. Journal Of Applied Physiology 2021, 131: 1444-1459. PMID: 34554016, PMCID: PMC8616606, DOI: 10.1152/japplphysiol.00286.2020.Peer-Reviewed Original Research