5.43 In Vitro Micro-Tissue and -Organ Models for Toxicity Te

5.43 In Vitro Micro-Tissue and -Organ Models for Toxicity Te

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时间:2019-08-06

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1、5.43InVitroMicro-Tissueand-OrganModelsforToxicityTestingZLi,ZyoxelLtd,Oxford,UK©2011ElsevierB.V.Allrightsreserved.5.43.1Introduction5515.43.2DevelopmentofInVitroTissueModels5525.43.2.1NaturalTissueModel(WholePerfusedOrganandTissueSlices)5525.43.2.2Cell-Based2DModel5525.43.2.2.1Pr

2、imarycells5535.43.2.2.2Cellline5535.43.2.2.32Dco-culture5535.43.2.3InVitro3DTissueModels5535.43.2.3.1Scaffold-freecellularspheroidmodels5535.43.2.3.2Scaffold-based3Dtissuemodels5545.43.2.3.33Dmicrofluidicmodels5545.43.2.3.4Stem-cell-derivedmodels5555.43.3ProgressinToxicityTesting

3、UsingInVitroMicro-TissueModels5555.43.3.1LiverModel5555.43.3.1.1Invitro2Dhepatocytemodels5565.43.3.1.2Perfusedlivermodels5575.43.3.1.3Liverslices5575.43.3.1.43Dtissuemodels5575.43.3.2NeuralModels5575.43.3.2.1Primarycells5585.43.3.2.2Celllines5585.43.3.2.3Neuralstemcells5585.43.3.

4、2.4Blood–brainbarrier(co-culture)model5585.43.3.2.5Spheroidmodels5585.43.3.2.6Brainslices5585.43.3.3CancerModels5595.43.3.3.12Dhumantumorcellmodels5595.43.3.3.2Rodentxenografts5595.43.3.3.3Multicellulartumorspheroidmodels5595.43.3.3.4Scaffold-basedcancermodels5595.43.3.3.5Stemcel

5、l-tumormodels5605.43.3.4CardiacModels5605.43.4CommercialDevelopmentofInVitroMicro-TissueModelsforToxicityTesting5605.43.5Summary560References562GlossaryorganotoxicityThedegreetowhichasubstancecangenotoxicityAdeleteriousactiononacell’sgeneticdamageanorgan.materialaffectingitsinteg

6、rity.parenchymalcellsThefunctionalcellsofanorganoridiosyncrasyDescribesanunusualindividualreactiontogland,asdistinguishedfromsupportingorconnectiveadrug.Nonidiosyncrasyisanantonym.tissue.Nonparenchymalcellisanantonym.morphogenesisThebiologicalprocessthatcausesanorganismtodevelopi

7、tsshape.5.43.1IntroductionDevelopinganewdrugfromresearchtomarketisalongandexpensiveprocesswhichtakesover10yearsandinvolvesdiscoveryaswellaspreclinicalandclinicaldevelopment.Thetotalcostsfromdiscoverytomarketlaunchareintherangeof$800millionforeachnewdrug[1].Approximately92%ofnewdr

8、ugsfailbetweenthepreclinicalandclinicald

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