Epithelial-stromal interactions in the adult bladder: Urothelial growth, differentiation, and maturation on culture fascsimiles of bladder stroma

摘要

Analysisoftheresponsivenessofisolatedadulturotheliumtoaseriesofdifferentstromalcell-extracellularmatrixcombinationsdemonstratedthecapacityofstromalcellstoinduceandmaintainnormalpatternsofurothelialgrowth,differentiation,andmaturationinvitro.Byincorporatingembryonicmesenchymalderived(Swiss3T3)cellsintotypeIcollagenmatrices,simplifiedthree-dimensionaltissue-likefacsimilesofbladderstromawerederived.Whenrecombinedwithsheetsofisolatedurotheliumthesefacsimilescouldapproximatelyreproducethecapacityofnaturalstromaltissuetosupporttheexpressionofnormalurothelialtissuespecificcharacteristics.Incontrastcoculturesbetweenurotheliaandmonolayersof3T3cells,appliedtothesurfaceofplanarcollagensubstratacouldonlypermiturothelialcellattachmentbutnotgrowthordifferentiationwhereaslethallyirradiated3T3(feeder)cells,undersimilarexperimentalconditions,couldsupportthemaintenanceofanimmatureorincompletelydifferentiatedurothelium.Conditionedmediumelaboratedbycultured3T3cellscouldnotstimulatefurtherdifferentiationinurotheliaculturedaloneonplanarcollagensubstrata.Thesestudiesindicatethatasignificantportionoftheregulatorycapacityofthestromainstromal-urothelialinteractionscanbeaccountedforbytheactivitiesofacloselyappliedpopulationofstromalcells,providedthecellsareviableandpresentedtotheurotheliuminathree-dimensionalcontextincombinationwithcollagen.Thecapacityofembryonicmesenchymalcellstoexpresspropertiesappropriatetothedevelopmentofamultilayeredterminallydifferentiatedurotheliumsuggeststhatnormalinteractionsbetweenadulturotheliumandstromaareoflimitedspecificitywiththeurotheliumrequiringanessentialinputofpermissivesignalsonly.