TheEpiIntestinaltissuemodel(SMI-100)offersnumerousadvantagesversuscurrentlyavailablepreclinicaltestingmodelssuchasCaco-2.Thehumancell-based3Dmodelincorporatesenterocytes,panethcell,Mcells,tuftcellsandintestinalstemcellsintoahighlydifferentiated, polarizedepithelium.TheEpiIntestinalFTtissue(SMI-100-FT)includesanunderlyinglaminapropriacontainingnormalhumanintestinalfibroblastsandisusefultostudyinflammation,woundrepair,innateimmuneresponses,andfibrosis.Bothtissuesareculturedattheair-liquidinterface(ALI)toallowphysiological(luminal)exposureconditions.EpiIntestinalrecapitulates manyaspectsofnormalintestinalfunctionincluding barrier,metabolism,inflammatoryandtoxicityresponses,similartonativehumanintestinaltissue.

ImportantfeaturesofEpiIntestinalincludethepresenceoffunctionaltightjunctionsandbrushbordersattheapicaltissuesurface. Invivo,brushbordersareindirectcontactwithluminalcontentsandincludeatleast22metabolicenzymesand19drugtransporters. EpiIntestinaltightjunctionsandbrushborderscloselymimichumanstructureandphysiology.

TheEpiIntestinal3DhumantissuemodelisroutinelyutilizedforscreeningpharmaceuticalsforarangeofendpointsincludingGItoxicityandinflammation,drugmetabolism,drugpermeation,fibrosis,andintestinalinfection.Straightforwardprotocolsandtheevaluationofearlymolecularandcellularendpointsoftenallowscientiststoacquiredataindays,notweeksormonths.

GIToxicity

UseEpiIntestinalforahighlypredictiveassaytoevaluateGItoxicityofpharmaceuticals.

GItoxicityreference

InflammationandFibrosis

UtilizeEpiIntestinal’shighlycontrolledinvitrocultureconditionstostudyintestinalinflammation,woundrepair,andfibrosis andassesstherapeuticeffects.

IntestinalInflammationReference

DrugDelivery&Metabolism

UtilizeEpiIntestinalforhighlypredictiveandhuman-relevantdrugdelivery. AssessAPIbioavailABIlity(influx)andeffluxtransport,drugmetabolism,anddrug-druginteractions. EpiIntestinalcanbeco-culturedwithotherphysiologicalsystems(e.g.livercells)inmicrofluidicsystemstoexaminetheeffectofdrugmetabolitesonGItoxicityortopredictdrugpermeation/absorptionviathe“luminal”sideofthetissue.

IntestinalDrugDeliveryReference

WoundRepair/EpithelialRestitution

UseEpiIntestinalFTtobetterunderstandmechanismsofwoundhealinginthegutandtoevaluatetherapeuticeffects.

IntestinalRestitutionReference

IntestinalInfection

UtilizeEpiIntestinaltostudyGItractinfection,host-pathogeninteractions,andinnateimmuneresponses.

BrowseourreferencelibrarytolearnmoreabouthowresearchershaveusedourEpiIntestinaltissueintheseareasofstudy.

Tissue:

Kit:SMI-100andSMI-100-FTEpiIntestinalkitsconsistof24individualtissues. SMI-196orSMI-196-FTEpiIntestinalkitsconsistof96tissuesinahighthroughputscreeningplate. Eachkit containstissues,culturemediumtosupportexperimentsfor24hours,andplasticware. PleasecontactMatTekforspecifickitcontents.

Formats:

• SMI-100andSMI-100-FT: Individualtissuesculturedincellcultureinserts.Dimensions: 9mmtissuediameter(surfacearea=0.6cm²),underlyingmicroporousmembraneporesize= 0.4μm
• SMI-196andSMI-196-FT: Tissuesgrownin96-wellhighthroughputscreeningplate. Dimensions: 0.19cmtissuediameter(surfacearea=0.11cm²). Underlyingmicroporousmembraneporesize=0.4μm

Culture:Air-liquidinterface

Lotnumbers:Tissuelotsproducedeachweekareassignedaspecificlotnumber.Aletterofthealphabetisappendedtotheendofthelotnumbertodifferentiatebetweenindividualsetsof24tissueswithinagivenproductionlotoftissues.Alltissuekitswithinaproductionlotareidenticalinregardstocells,medium,handling,cultureconditions,etc.

Shipment:At4°Conmedium-supplemented,agarosegels

Shipmentday:EveryMonday

Delivery:TuesdaymorningviaFedExpriorityservice(US).OutsideUS:Tuesday-Wednesday dependingonlocation.

Shelflife:Includingtimeintransit,tissuesmaybestoredat4°Cforupto2dayspriortouse.However,thebestreproducibilitywillbeobtainediftissuesareusedconsistentlyonthesameday,e.g.Tuesdayafternoonorfollowingovernightstorageat4°C(Wednesdaymorning).

Lengthofexperiments:TissueculturescanbecontinuedforONE(1)MONTHormorewithgoodretentionofnormalmorphology.Tissuesmustbefedeveryotherdaywith5.0mlofmaintenancemedium(SMI-100-MM).Cellcultureinsertsareplacedatopwashers(EPI-WSHR)orculturestands(MEL-STND)in6-wellplatestoallowuseof5.0ml.

Cells:

Type:Primaryhumansmallintestinalepithelialcells(HSIE)

Geneticmake-up:Singledonor

Derivedfrom:Healthyadultdonor

Alternatives:Alternatedonorsavailableuponrequest

Screenedfor:HIV,Hepatitis-B,Hepatitis-C,mycoplasma

Medium:

Basemedium:Dulbecco’sModifiedEagle’sMedium(DMEM)

Growthfactors/hormones:Epidermalgrowthfactorandotherproprietaryfactors

Antibiotics:Gentamicin5µg/ml

Anti-fungalagent:AmphotericinB0.25µg/ml

pHIndicator:Phenolred

Otheradditives:Proprietary

Alternatives:Phenolred-free,antibiotic-free,anti-fungal-freemediumandtissuesareavailable.Agentsareremovedatleast3dayspriortoshipment.

QualityControlandSterility:

Visualinspection:Alltissuesarevisuallyinspectedandifphysicalimperfectionsarenoted,tissuesarerejectedforshipment

Sterility:Allmediausedthroughouttheproductionprocessischeckedforsterility.Maintenancemediumisincubatedwithandwithoutantibioticsfor1weekandcheckedforsterility.Theagarosegelfromthe24-wellplateusedforshippingisalsoincubatedfor1weekandcheckedforanysignofcontamination

Screeningforpathogens:AllcellsarescreenedandarenegativeforHIV,hepatitisBandhepatitisCusingPCR.However,noknowntestmethodcanoffercompleteassurancethatthecellsarepathogenfree.Thus,theseproductsandallhumanderivedproductsshouldbehandledatBSL-2levels(biosafetylevel2)orhigherasrecommendedintheCDC-NIHmanual,“BiosafetyinmicroBIOLOGicalandbiomedicallaboratories,”1998.Forfurtherassistance,pleasecontactyoursiteSafetyOfficerorMatTektechnicalservice

Notificationoflotfailure:IfatissuelotfailsQCorsterilitytesting,thecustomerwillbenotifiedandthetissueswillbereplacedwithoutcharge.BecauseourQCandsterilitytestingisdonepost-shipment,notificationwillbemadeassoonaspossIBLe(Undernormalcircumstances,ET-50failureswillbenotifiedbyThursday5p.m.;sterilityfailureswillbenotifiedwithin8daysofshipment)