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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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1 2 3
Stage25AVcushionsinlumenoftubescaffold
Day2
TheAllNewandImprovedFLOWMASTER3000!!!(JohnWeidner,USC)
FreeEdge
TenascinCexpressionandlocalizaMonregulatedbyFlowandRhoA
HongTan
FlowandRhoAcanregulatethematerialproperMesofdevelopingvalvesasmeasuredbyAtomicForceMicroscopy
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ulus(P
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NoFlow Flow Floww/y‐compound Floww/LPA
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Force(nN)
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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