Quantification of Three-Dimensional Cell-Mediated Collagen Remodeling Using Graph Theory 英文参考文献.docVIP

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Quantification of Three-Dimensional Cell-Mediated Collagen Remodeling Using Graph Theory 英文参考文献.doc

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Quantification of Three-Dimensional Cell-Mediated Collagen Remodeling Using Graph Theory 英文参考文献

QuantificationofThree-DimensionalCell-Mediated CollagenRemodelingUsingGraphTheory CemalCagatayBilgin1,AmandaW.Lund2,AliCan3,GeorgeE.Plopper2,Bu¨lentYener1* 1ComputerScienceDepartment,RensselaerPolytechnicInstitute,Troy,NewYork,UnitedStatesofAmerica,2BiologyDepartment,RensselaerPolytechnicInstitute,Troy, NewYork,UnitedStatesofAmerica,3GeneralElectricGlobalResearchCenter,Niskayuna,NewYork,UnitedStatesofAmerica Abstract Background:Cellcooperationisacriticaleventduringtissuedevelopment.Wepresentthefirstprecisemetricstoquantify the interaction between mesenchymal stem cells (MSCs) and extra cellular matrix (ECM). In particular, we describe cooperative collagen alignment process with respect to the spatio-temporal organization and function of mesenchymal stemcellsinthreedimensions. Methodology/PrincipalFindings:Wedefinedtwoprecisemetrics:CollagenAlignmentIndexandCellDissatisfactionLevel, for quantitatively tracking type I collagen and fibrillogenesis remodeling by mesenchymal stem cells over time. Computationofthesemetricswasbasedongraphtheoryandvectorcalculus.ThecellsandtheirthreedimensionaltypeI collagenmicroenvironmentweremodeledbythreedimensionalcell-graphsandcollagenfiberorganizationwascalculated from gradient vectors. With the enhancement of mesenchymal stem cell differentiation, acceleration through different phaseswasquantitativelydemonstrated.Thephaseswereclusteredinastatisticallysignificantmannerbasedoncollagen organization, with late phases of remodeling by untreated cells clustering strongly with early phases of remodeling by differentiating cells. The experiments were repeated three times to conclude that themetrics could successfully identify criticalphasesofcollagenremodelingthatweredependentuponcooperativitywithinthecellpopulation. Conclusions/Significance:Definitionofearlymetricsthatareabletopredictlong-termfunctionalitybylinkingengineered tissuestructuretofunctionisanimportantsteptowardoptimizingbiomaterialsforthepurposesofregenerativemedicine. Citati