35602 6IsletTransplantationβCellReplacementTherapiesforDiabetes.docx
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35602 6IsletTransplantationβCellReplacementTherapiesforDiabetes.docx
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356026IsletTransplantationβCellReplacementTherapiesforDiabetes
JournalofTransplantation
IsletTransplantation&β-CellReplacementTherapiesforDiabetes
GuestEditors:
AntonElloPilEggi,ThiERRyBerney,OUeKoRsgREn,AndAndREwPqsseIt
Copyright©2011HindawiPublishingCorporation.Allrightsreserved.
Thisisaspecialissuepublishedin“JournalofTransplantation.”AllarticlesareopenaccessarticlesdistributedundertheCreativeCom-monsAttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
EditorialBoard
GianLuigiAdani,ItalyRichardAllen,AustraliaJosephF.Buell,USA
P.Burra,Italy
DiegoCantarovich,FranceDenisCastaing,FranceGaetanoCiancio,USA
F.H.J.Claas,TheNetherlandsWaldoConcepcion,USA
J.V.Conte,USA
JohnH.Dark,UK
R.Davis,USA
AmritaDosanjh,USA
R.Duquesnoy,USA
NilooM.Edwards,USA
YuriGenyk,USA
K.A.V.Hockerstedt,FinlandAshokkumarJain,USA
BruceKaplan,USA
R.L.Kormos,USA
BernhardK.Kr¨amer,GermanySheriM.Krams,USA
PaulC.Kuo,USA
RaymondH.Liang,HongKongMalekG.Massad,USA
ShujiMiyagawa,Japan
P.S.Randhawa,USA
CamilloRicordi,USA
SimonRobson,USA
WojciechRowi´nski,PolandJohnPaulScott,USA
LindaSher,USA
HavalShirwan,USA
A.JosephTector,USA
EricThervet,France
GiuseppeTisone,Italy
G.Tufveson,Sweden
RamanV.Venkataramanan,USATrevorWilliams,AustraliaKazuhikoYamada,USA
NorioYoshimura,JapanAndreasZuckermann,Austria
Contents
Chapter1IsletTransplantation&p-CellReplacementTherapiesforDiabetes,ThierryBerney,OlleKorsgren,AndrewPosselt,andAntonelloPileggiVolume2011,ArticleID157840,2pages
Chapter3StriatedMuscleasImplantationSiteforTransplantedPancreaticIslets,DanielEspes,OlofEriksson,
JoeyLau,andPer-OlaCarlssonVolume2011,ArticleID352043,6pages
Chapter4CurrentStatusofImmunomodulatoryandCellularTherapiesinPreclinicalandClinicalIsletTransplantation,PreetiChhabraandKennethL.BraymanVolume2011,ArticleID637692,24pages
Chapter5Evolutionofp-CellReplacementTherapyinDiabetesMellitus:
IsletCellTransplantation,CyrusJahansouz,CameronJahansouz,SeanC.Kumer,andKennethL.BraymanVolume2011,ArticleID247959,21pages
Chapter6MolecularImaging:
APromisingTooltoMonitorIsletTransplantation,PingWang,ZdravkaMedarova,andAnnaMooreVolume2011,ArticleID202915,14pages
Chapter10PancreasProcurementandPreservationforIsletTransplantation:
PersonalConsiderations,
HirofumiNoguchi
Volume2011,ArticleID783168,7pages
Chapter1Editorial
IsletTransplantation&/β-CellReplacementTherapiesforDiabetes
ThierryBerney,1OlleKorsgren,2AndrewPosselt,3andAntonelloPileggi4
DepartmentofSurgery,GenevaUniversityHospitals,1211Geneva,Switzerland2DepartmentofClinicalImmunology,UppsalaUniversityHospital,75185Uppsala,Sweden
DepartmentofSurgery,UniversityofCalifornia,SanFrancisco,CA94143,USA
DepartmentsofSurgery,BiomedicalEngineering,MicrobiologyandImmunology,DiabetesResearchInstitute,
UniversityofMiami,Miami,FL33136,USA
CorrespondenceshouldbeaddressedtoAntonelloPileggi,apileggi@med.miami.edu
Received23January2012;Accepted23January2012
Copyright©2011ThierryBerneyetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
Restorationofphysiologicmetaboliccontrolistheultimatetherapeuticgoalforpatientswithdiabetesbutisdifficulttoachievebymeansofmedicaltherapy.TransplantationofisletsofLangerhansrepresentsaviabletherapeuticoptionforpatientswithinsulin-dependentdiabetes.Itiscurrentlyofferedtopatientswithabrittleformofdiabetesandhypoglycemiaunawareness.Currentlimitationsofislettransplantationincludescarcityofdeceaseddonorpancreata,partiallyeffectiveisletisolationandpurificationprotocols,needforlife-longsystemicimmunosuppression,inadequateimplantationsites,lackofpredictivetests,andnoninvasivegraftmonitoringprotocols.
Greatprogresshasbeenrecordedindifferentresearchareasaimedatovercomingcurrentlimitationsofisletcelltransplantation.Theseareasincludestemcellstechnology,xenotransplantation,developmentofnovelimmunosuppressiveregimens,immunetolerance,immunoisolationprotocols,alternativesitesforisletimplantation,immunemonitoring,andnoninvasiveimagingtechniques.Thisspecialissuewasopentothescientificcommunityworkingonthedevelopmentofbeta-cellreplacement.Oftheseveralpapersreceived,tenreceivedfavorablepeerreviewsandwereselectedforpublicationinthisissuetocoverspecifictopicsofgeneralinterestinthisfield.
ThepaperbyC.Jahansouzetal.providesacomprehensiveandhistoricaloverviewofbeta-cellreplacementtherapies.ThepaperbyP.ChhabraandK.L.Braymanreviewsemergingclinicalandpreclinicalapproachestowardenhancingtheclinicaloutcomeofisletcelltransplantationandincludesaspectsrelatedtocytoprotectionandimmuneinterventions.ThepaperbyH.Wangetal.isfocusedonimportantcytoprotectivepathwayssuchascarbonmonoxideandhemeoxygenase-1andtheirabilitytoenhanceisletcellviabilityandengraftment.ThepaperbyX.Wangetal.offersaperspectiveontheB7-H4co-stimulationpathwayanditspotentialtowardenhancingimmuneregulationandprolongingisletgraftsurvival.
Recognizingthecurrentlimitationsofhumanpancreasdonationafterbraindeath,alternativecellular-basedapproachesareactivelybeingexploredtowidentheclinicalapplicationofbeta-cellreplacementtherapies.ThepaperbyM.R.Hammermanprovidesinterestingnewexperimentaldataonporcineisletcellengraftmentinxenogeneicrecipientswithoutimmunosuppression.InhispaperH.Noguchisharesanoverviewofhisexperiencewithnovelprotocolsaimedatamelioratingpancreaspreservationinjuryandimprovingtheyieldandqualityofisletsobtainedfortransplantation.I.Meivar-Levyetal.exploretheuseofhepaticcellsexpressingalbuminandmesenchymalpropertiesthathavebeenengineeredtoproduceinsulinasanalternativeandpotentiallyunlimitedsourceoftransplantableinsulin-producingcells.F.Carlottietal.assesstheimportantissueoftheprosandconsrelatedtothetranslatabilityofresultsobtainedinrodentstudiestohumanswhenstudyingbetacellregeneration.
Thereareincreasingeffortsaimedatdevelopingnovelimplantationsitesforisletcells.ThepaperbyD.Espes
etal.describesthepromisingpropertiesofintramuscularsitewhichmakesofitaviableoptionforisletcellimplantation.
P.Wangetal.reviewtheimportantandrapidlyevolvingfieldinvivoisletimaging.Theuseofmolecularimagingtechniquesmaybeofinvaluableassistancetowardmonitoringisletgraftsaswellasatooltobetterunderstandthephysiopathologicalchangesthatoccuraftertransplantation.
ThierryBerneyOlleKorsgrenAndrewPosseltAntonelloPileggi
HindawiPublishingCorporationJournalofTransplantationVolume2011,ArticleID637692,24pagesdoi:
10.1155/2011/637692
Chapter4ReviewArticle
CurrentStatusofImmunomodulatoryandCellularTherapiesinPreclinicalandClinicalIsletTransplantation
PreetiChhabra1andKennethL.Brayman1,2,3
DepartmentofSurgery,UniversityofVirginia,Charlottesville,VA22908,USA
DivisionofTransplantation,DepartmentofSurgery,UniversityofVirginia,Charlottesville,VA22908,USA
TheCenterforCellularTransplantationandTherapeutics,UniversityofVirginia,Charlottesville,VA22908,USA
CorrespondenceshouldbeaddressedtoKennethL.Brayman,klb9r@hscmail.mcc.virginia.eduReceived1May2011;Accepted11July2011AcademicEditor:
AntonelloPileggi
Copyright©2011P.ChhabraandK.L.Brayman.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
Clinicalislettransplantationisaf-cellreplacementstrategythatrepresentsapossibledefinitiveinterventionforpatientswithtype1diabetes,offeringsubstantialbenefitsintermsofloweringdailyinsulinrequirementsandreducingincidencesofdebilitatinghypoglycemicepisodesandunawareness.Despiteimpressiveadvancesinthisfield,alimitingsupplyofislets,inadequatemeansforpreventingisletrejection,andthedeleteriousdiabetogenicandnephrotoxicsideeffectsassociatedwithchronicimmunosuppressivetherapyprecludeitswide-spreadapplicability.Islettransplantationhoweverallowsawindowofopportunityforattemptingvarioustherapeuticmanipulationsofisletspriortotransplantationaimedatachievingsuperiortransplantoutcomes.Inthispaper,wewillfocusonthecurrentstatusofvariousimmunosuppressiveandcellulartherapiesthatpromotegraftfunctionandsurvivalinpreclinicalandclinicalislettransplantationwithspecialemphasisonthetolerance-inducingcapacityofregulatoryTcellsaswellasthejS-cellsregenerativecapacityofstemcells.
Introduction
Type1diabetes(T1D)isaT-cell-mediatedautoimmunediseasethatinvolvestheprogressivedestructionofpancreaticfcellsresultingincompletelossofinsulinsecretion[1].Whileacombinationofgeneticpredispositionandautoimmuneprocessescontributestoitsdevelopment,inflammatorymediatorsandinnateimmunityplayakeyroleintheinductionandamplificationoftheimmuneassaultaswellasinthemaintenanceofinsulitis[2,3].Basedonstudiesusinganimalmodelsofautoimmuned
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