GrowingCardiovascularTissuesInVitroRichGoodwin,PhD

CellBiologyandAnatomyUSCSchoolofMedicine

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Lumen

Day21Cardiotube

EmbryonicMouseCardiacMyocytesat11DaysofCulture

TEMsofTubeCulturedCardiacMyocytesUndergomyofibrillogenesisanddevelopmentcell‐celljuncMons

Evansetal,2003

WeareusingcardiotubestotestmechanismsofcardiovasculardevelopmentsuchasTetralogyofFallot(Dr.Kheradvar).ToxicityScreening(Dr.Yost/Biotech)

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Stage25AVcushionsinlumenoftubescaffold

Day2

TheAllNewandImprovedFLOWMASTER3000!!!(JohnWeidner,USC)

FreeEdge

TenascinCexpressionandlocalizaMonregulatedbyFlowandRhoA

HongTan

FlowandRhoAcanregulatethematerialproperMesofdevelopingvalvesasmeasuredbyAtomicForceMicroscopy

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NoFlow Flow Floww/LPA Floww/y‐compound

(P<0.05)HongTan,StefBiechler,andDr.Dean(Clemson)

ValveConclusions•  ExpressionofFibrousECMproteinscanberegulatedbyflow.

•  WehypothesizethatthemechanicalforcescreatedbypulsaVleflowdeformthecytoskeletonandacVvatetheRhoApathway.

•  ExperimentalmanipulaVonoftheRhoApathwaydoesregulateFibrousECMexpressionandlocalizaVonindevelopingvalves

So,ifyouwanttomakestrongervalvesfaster,useFlowandRhoA

CoronaryDevelopment

A.TsiarasInLifeAug.26th,2005

ManyThanks:JDPodsandMJYost‐USCSOM

BobPrice‐USCIRF

MyLabHJEvans‐Anderson–AlumnusStefanieBiechlerLorainJunorAndreaRobertsSamanthaSMnsonHongTan

USCEngineeringJohnWeidner,ArashKheradvar

MUSCRogerMarkwaldChipNorris

Northwestern:BobDedman

NIHSupportCobreP20‐RR1634(RRM)R21HL080294(RLG)RO1HL086856(RLG)NSFRIIBridge

Clemson:DelphinDean

KeyPoints:• ThemechanismsofcardiovasculardevelopmentcaninvesMgatedusing3Dculturingtechniques.• DevelopmentalmechanismsarelikelytobeimportantduringregeneraMon.

Problems:• ThetransiMonfromcapillarytolargercaliberbloodvesselshasbeendifficulttomodel.• Numerousothers.

CollaboraMons:• ClinicalapplicaMons.• Gratefulformypresentcollaborators