Hepatocyte Transplantation: Methods and Protocols

240 Pages·2009·3.25 MB·English

by  Juliana Puppi

Hepatocyte Transplantation
M E T H O D S I N M O L E C U L A R B I O L O G Y TM
John M. Walker, SERIES EDITOR
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M M B TM
E T H O D S I N O L E C U L A R I O L O G Y
Hepatocyte Transplantation
Methods and Protocols
Edited by
Anil Dhawan
King’s College Hospital, London, UK
Robin D. Hughes
King’s College London, School of Medicine
London, UK
Editors
AnilDhawan RobinD.Hughes
King’sCollegeHospital King’sCollegeLondon
London,UK SchoolofMedicine
[email protected] London,UK
[email protected]
SeriesEditor
JohnM.Walker
UniversityofHertfordshire
Hatfield,Herts.
UK
ISBN:978-1-58829-883-6 e-ISBN:978-1-59745-201-4
ISSN:1064-3745 e-ISSN:1940-6029
DOI10.1007/978-1-59745-201-4
LibraryofCongressControlNumber:2008939645
#HumanaPress,apartofSpringerScienceþBusinessMedia,LLC2009
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Preface
Cellular therapy using human hepatocytes is being evaluated worldwide as an
alternativetoorgantransplantationinpatientswithliver-basedmetabolicdiseaseand
acuteliverfailure.Thebasisforclinicalusehascomefromthedemonstrationofefficacy
inanimalmodelsofacuteandchronicliverdisease.
Protocols have been developed for the isolation of hepatocytes from liver tissue
under GMP conditions and also for improved methods of cryopreservation, so hepa-
tocytes can be stored for later clinical use. Assays are used to assess the quality and
function of the hepatocytes prior to transplantation. There are clinical protocols for
administrationofcellsdirectlyintothepatient’sliver.
The engraftment of donor cells in the recipient liver can be detected by DNA
techniquesorfunctionalproteinsinthecaseofgeneticliverdisorders.Invivomethods
areneededtotrackthefateofhepatocytesaftertransplantation.
Due to the shortage of donor organs,thefuture of hepatocyte transplantation will
be alternative sources of liver cells such as foetal hepatoblasts or stem cell-derived
hepatocytes. Methods for culture and in vitro proliferation of stem cells will be
importantfortheirapplication.
Itishopedthatthisvolumefromtheexpertsinthefieldprovidesthereaderwiththe
practicalprotocolstoenablethemtoperformandinvestigatehepatocytetransplanta-
tion. Needless to say this is a rapidly developing field, and new and improved techni-
quesarebeingdevelopedallthetime.
AnilDhawan&RobinD.Hughes
v
Acknowledgements
To my wife Anita and boys Atin and Ashish for their understanding, love and
supportthattheyhaveprovidedthroughoutmycareer.
Sincerethankstoallthecontributors.
Particular thanks to Professor Nigel Heaton, Mr Mohamed Rela, Liver Transplant
Coordinators,andDrRagaiMitryforhelpingestablishthehepatocytetransplantation
programmeatKing’sCollegeHospital.
AnilDhawan
vii
Contents
Preface..............................................................v
Acknowledgements ....................................................vii
Contributors......................................................... xi
ColorPlates .........................................................xv
1 HumanHepatocyteTransplantationOverview ...........................1
JulianaPuppiandAnilDhawan
2 IsolationofHumanHepatocytes.....................................17
RagaiR.Mitry
3 AnOptimisedMethodforCryopreservationofHumanHepatocytes .........25
ClaireTerryandRobinD.Hughes
4 LiverCellCultureTechniques.......................................35
Jose´ V.CastellandMarı´aJose´ Go´mez-Lecho´n
5 InVitroAssaysforInductionofDrugMetabolism .......................47
BrianG.Lake,RogerJ.Price,AmandaM.Giddings,
andDavidG.Walters
6 HepatocyteApoptosis .............................................59
MustaphaNajimi,Franc¸oiseSmets,andEtienneSokal
7 SmallAnimalModelsofHepatocyteTransplantation .....................75
JurgenSeppen,EbtisamElFilali,andRonaldOudeElferink
8 HepatocyteTransplantationTechniques:LargeAnimalModels .............83
AnneWeber,Marie-The´r`eseGroyer-Picard,andIbrahimDagher
9 CellTransplantTechniques:EngraftmentDetectionofCells ...............97
RobertA.FisherandValeriaR.Mas
10 HepaticPreconditioningforTransplantedCellEngraftment
andProliferation ................................................107
Yao-MingWuandSanjeevGupta
11 ExVivoGeneTransferintoHepatocytes..............................117
XiaWang,PrashantMani,DebiP.Sarkar,NamitaRoy-Chowdhury,
andJayantaRoy-Chowdhury
12 SourcesofAdultHepaticStemCells:Haematopoietic ...................141
RosemaryJeffery,RichardPoulsom,andMalcolmR.Alison
13 ProductionofHepatocyte-LikeCellsfromHumanAmnion...............155
ToshioMiki,FabioMarongiu,EwaC.S.Ellis,KenDorko,
KeitaroMitamura,AaratiRanade,RobertoGramignoli,
JulioDavila,andStephenC.Strom
14 GenerationofHepatocytesfromHumanEmbryonicStemCells ...........169
NiloufarSafiniaandStephenLMinger
ix
x Contents
15 Isolation,InVitroCultivationandCharacterisationofFoetal
LiverCells .....................................................181
YueWu,ChetanC.Shatapathy,andStephenL.Minger
16 HumanIntrahepaticBiliaryEpithelialCellLineages:StudiesInVitro .......193
RuthJoplinandStiveliaKachilele
17 LiverCellLabellingwithMRIContrastAgents ........................207
MichelModo,ThomasJ.Meade,andRagaiR.Mitry
18 MicrobiologicalMonitoringofHepatocyteIsolationintheGMP
Laboratory.....................................................221
SharonC.Lehec
Index.............................................................229
Contributors
MALCOLMR.ALISON.CentreforDiabetesandMetabolicMedicine,ICMS,Bart’sand
TheLondonSchoolofMedicine,London,UK
JOSE´ V.CASTELL.UnitofExperimentalHepatology,UniversityHospital‘‘LaFe’’,
Valencia,Spain
IBRAHIMDAGHER.InsermU804;UniversityParis-Sud,HoˆpitaldeBiceˆtre,
Kremlin-Biceˆtre,andServicedeChirurgieGe´ne´rale,HoˆpitalBe´cl`ere,Clamart,
France
JULIODAVILA.Pfizer,Inc.,St.LouisMo,USA
ANILDHAWAN.PaediatricLiverCentre,King’sCollegeHospital,DenmarkHill,
London,UK
EBTISAMELFILALI.AMCLivercenter,Amsterdam,TheNetherlands
KENDORKO.DepartmentsofPathologyandSurgeryandMcGowanInstitute
forRegenerativeMedicine,UniversityofPittsburgh,USA
EWAC.S.ELLIS.DepartmentsofPathologyandSurgeryandMcGowanInstitute
forRegenerativeMedicine,UniversityofPittsburgh,USA
ROBERTA.FISHER.DepartmentofSurgery,TransplantationDivision,Virginia
CommonwealthUniversity,MedicalCollegeofVirginiaHospitals,Richmond,
Virginia,USA
DOMINIQUEFRANCO.InsermU804;UniversityParis-Sud,HoˆpitaldeBiceˆtre,
Kremlin-Bicˆetre,andServicedeChirurgieGe´ne´rale,HoˆpitalBe´cl`ere,Clamart,France
AMANDAM.GIDDINGS.BIBRAInternational,Carshalton,SurreyandCentrefor
Toxicology,FacultyofHealthandMedicalSciences,UniversityofSurrey,Guildford,
UK
MAR´IAJOSE´ GO´MEZ-LECHO´N.UnitofExperimentalHepatology,UniversityHospital‘‘La
Fe’’,Valencia,Spain
ROBERTOGRAMIGNOLI.DepartmentsofPathologyandSurgeryandMcGowanInstitute
forRegenerativeMedicine,UniversityofPittsburgh,USA
MARIE-THE´RE`SEGROYER-PICARD.InsermU804;UniversityParis-Sud,HoˆpitaldeBiceˆtre,
Kremlin-Biceˆtre,France
SANJEEVGUPTA.MarionBessinLiverResearchCenter,DiabetesCenter,CancerResearch
Center,DepartmentsofMedicineandPathology,andInstituteforClinicaland
TranslationalResearch,AlbertEinsteinCollegeofMedicine,NewYork,USA
ROBIND.HUGHES.InstituteofLiverStudies,King’sCollegeLondonSchoolofMedicine,
London,UK
ROSEMARYJEFFERY.HistopathologyUnit,CancerResearchUK,LondonResearch
Institute,London,UK
RUTHJOPLIN.LiverResearchLaboratories,InstituteofBiomedicalResearch,University
ofBirminghamMedicalSchool,Birmingham,UK
xi