Stem Cells PDF
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Handbook of Experimental Pharmacology Volume 174 Editor-in-Chief F.Hofmann,München EditorialBoard J.Beavo,Seattle,WA D.Ganten,Berlin M.Michel,Amsterdam C.Page,London W.Rosenthal,Berlin AnnaM W. obus KennethR B. oheler (cid:127) Editors StemC ells Contributors M.R. Alison, C. Badorff, N. Benvenisty, B. Berninger, N. Beyer Nardi, A. Branzi, M. Brittan, P. Budde, G.A. Colvin, H. Darr, C. Denning, S. Dimmeler, F. Dönmez, M.S. Dooner, R. Enseñat-Waser, L.J. Field, M. Götz, G. Grenier, M. Hack, R. Harris, J. Jones, T. León-Quinto, M. Lovell, C. Mummery, R. Passier, G. Paul, P.J. Quesenberry, J.A. Reig, E. Roche, S. Rose-John, M. Rubart, M.A. Rudnicki, H. Sauer, L. da Silva Meirelles, B. Soria, N.D. Theise, C. Ventura, M. Wartenberg, G. Weitzer, N.A. Wright 123 Professor Kenneth R. Boheler, PhD Anna M. Wobus, PhD Investigator In Vitro Differentiation Group Laboratory of Cardiovascular Science Dept. of Cytogenetics Gerontology Research Program Leibnitz Institute of Plant Genetics National Institute on Aging, NIH and Crop Plant Research (IPK) 5600 Nathan Shock Drive Corrensstr. 3 Baltimore, MD 21224 D-06466 Gatersleben U SA Germany [email protected] [email protected] ISBN:978-3-540-77854-7 HandbookofExperimentalPharmacologyISSN0171-2004 LibraryofCongressControlNumber:2008920054 (cid:1)c Springer-VerlagBerlinHeidelberg2008 Thisworkissubjecttocopyright. 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CoverDesign:WMXDesignGmbH,Heidelberg Printedonacid-freepaper 9 8 7 6 5 4 3 2 1 springer.com Preface Significant advances in stem cell research and their potentials for therapeu- tic applications have attracted the attention of the scientific community and capturedtheimaginationofsocietyasawhole.Notsolongago,thestudyof moststemcells,otherthanthosethatregeneratedthehaematopoieticsystem, wasratherobscureandlimitedtoarelativelysmallnumberofresearchersand laboratories. The uproar over stem cells really began in 1998 with the suc- cessful derivation of pluripotent human embryonic stem (ES) cells by James Thomsonandco-workers.Thisbreakthroughandthesubsequentgeneration of specialized human cells in vitro led to a paradigm shift within the scien- tificcommunity,whichtransformedthisspecializedendeavourfromatopicof scientificinteresttoalineofinvestigationwiththepotentialtogeneratecellsca- pableoftreatingseriousailments,includingdiabetes,cardiovasculardiseases andneurodegenerativedisorders.Thusthedawnofregenerativemedicinehas spawnedfromthesomewhatesotericstudyofstemcells. Since1998,extensiveresearchendeavourshavebeendevotedtothestudyof bothembryonicandadultstemcells.Earlyreportssuggestedthatadultstem cellshadahigherplasticitythanpreviouslybelieved,perhapsevencomparable withthatdemonstratedbyembryonicstemcells,butseveralobservationsof the so-called transdifferentiation capacity and plasticity of adult stem cells havenotbeenrepeated.Thesereports,however,encouragedon-goingdebates about the capacity of adult versus embryonic stem cells and their potential useinregenerativemedicine.Althoughattimescontroversial,theseresearch effortsledtoabetter,althoughstilllimited,understandingofstemcellswith respecttotheiridentification,isolation,anddevelopmentalcapacities. Importantly, stem cells do not represent static entities that do not differ between embryosand adults. In fact, embryonic stem cellsin early embryos represent basic units of life in higher organisms, while adult stem cells in somatic tissues represent cellular stores capable of regenerating tissue and maintainingorganfunctions.Regardlessofthesedifferencesinpotential,all stem cells derived from the embryo or adult are characterized by unique propertiesthatpermitaccuratecellcopyinginvivoinaprocesstermedself- renewal. Additionally, all stem cells retain the capacity to differentiate into more mature cell types. It is the degree of self-renewal and differentiation potentialthatdiffersamongthevariousstemcellpopulationsandcelllines. VI Preface These common traits have led to vigorous scientific and ethical debates, whicharelikelytopersistformanyyears.Addingtothescientificandethical dilemmassurroundingstemcellswasthesuccessfultransferofhumansomatic nucleiintofertilizedhumanoocytesinaprocessknownasnucleartransfer(nt), andthecreationthroughaprocessknownastherapeuticcloningofhumanntES celllinesbySouthKoreanscientistsin2004.Thishasrecently(May2005)been followed by the efficient generation of patient-derived ntES cell lines, which willlikelyinfluencetheethicaldebateandgrowthofstemcellresearchinthe future.Forthefirsttimeandasaconsequenceofthesedevelopments,stemcell research coupled with molecular biology and tissue engineering techniques constituteapotentialbasisforrationaltherapeuticstrategiesofregenerative medicine.Moreover,humanES-derivedsomaticcellsmayrepresentinnovative pharmacologicaltoolsfordrugscreening,theidentificationofnewdrugtargets and cell-based compound delivery systems. Finally, these cells may facilitate anunravellingofthehithertoinaccessibleparadigmsofhumandevelopment. In2004,duringoneofthemostcontentiousperiodsofdebatewithrespect to the scientific, ethical and legal issues of stem cell research, the Board of Editors at the Handbook of Experimental Pharmacology approached us to editaspecialvolumedevotedtostemcells.Theideawasattractivebecauseit wouldgiveusthechancetosolicitandcombineinonevolumeabodyofwork encompassingtherapidlyadvancingdevelopmentsofstemcellresearchwith astate-of-the-artviewofstemcellbiology.Weinvitedleadingexpertsinthe fields of embryonic and adult stem cells to submit chapters for this volume, andalthoughitprovedimpossibleforeveryonetosubmitamanuscriptwithin thedesignatedtimeframe,thisvolumeisacompilationoftheirandourefforts toassembleanoverviewoftheimportantaspectsandissuessurroundingstem cellresearch. The first two chapters are dedicated to molecular mechanisms regulating self-renewalanddifferentiationofhuman(DarrandBenvenisty)andmouse (Weitzer) ES cells. In the latter, the author describes how ES cell research, throughtheinvitrouseoftheembryoidbodymodel,reflectsearlydevelop- mentalprocessesinvivo(Weitzer),andinthefollowingcontribution,Warten- berg et al. demonstrate how the in vitro model system can be employed for the study of angiogenesis and tumour-induced angiogenesis. The following chaptersreviewthepresentstateofknowledgewithrespecttomouseandhu- manEScell-derivedcardiac(RubartandField;Passieretal.)andpancreatic (Roche et al.) cells and their potential application in tissue repair of heart diseasesanddiabetes,respectively.VenturaandBranzidescribeautocrineand intracrinesignallingpathwaysimplicatedinES-derivedcardiogenesisandhow pharmacologicalapproachesmayfacilitatethisprocess. Thesubsequentchaptersdealmainly,butnotexclusively,withadultstem cells,andtheauthorsdiscussmechanismsandpotentialapplicationsofthese cellsinregenerativemedicine.Auniqueconceptofstemcellregulationbased onhaematopoieticstemcells(Quesenberryetal.)andadetailedoverviewthat Preface VII reflects the importance of markers in adult tissue-based stem cells (Alison etal.)aretheperfectintroductiontothissetofchapters.Next,thechaptersde- scribehowhaematopoieticstem/progenitorcells(Rose-John)ormesenchymal stemcells(BeyerNardianddaSilvaMeirelles)isolatedfrombonemarrowmay beisolatedandmanipulatedbyexvivoexpansionfortissueregeneration.Neo- vascularizationandcardiacrepairbybonemarrow-derivedstemcells(Badorff andDimmeler)andtheuseofdifferentstem/progenitorcellsformyogenictis- suerepair(GrenierandRudnicki)arethetopicsofthefollowingcontributions. Neuralstemcells,theirpropertiesandimplicationsforthetreatmentofneu- rodegenerative diseases are extensively describedand criticallydiscussedby Berninger,HackandGötz.Theexperimentalstudiesdescribedinthespecial issuearethencomplementedbyadetaileddescriptionofthepresentstateofa stemcelltherapywithrespecttopatientswithParkinson’sdisease(Paul). Toendthisspecialvolume,wehaveselectedachapterdedicatedtothefuture of stem cell research. Theise and Harris present a stimulating discussion on how unexpected and controversial findings of adult stem cell research may openupnewperspectivestofosterourunderstandingofcellbiology. Wearedeeplygratefultoallthecontributorsfortheiractiveparticipation and significant contributions to this volume. We are aware that this volume could not and does not cover all topics and aspects of stem cell research. In fact, and during the past few years, stem cell research has metamorphosed intodistinctandspecializedavenuesofresearch;however,webelievethatthis volumepresentsinasinglebookmanynovelaspectsofstemcellbiologywith respecttoscientificendeavoursandfutureapplications.Ofparticularnoteare the pharmacologicalissuesthat have been compiled, whichhave never been adequatelyaddressedinthepast. WealsowouldliketothankMrs.SusanneDathe,deskeditorbiomedicine atSpringer,andMrs.KathrinSeiffert,IPKGatersleben,fortheirsupportand experteditorialhelp. Inconclusion,wehopethatthisvolumewillbevaluedbyresearchersinthe field, and by those who are engaged in the future developments of stem cell researchandtheapplicationsofstemcellsinregenerativemedicine. Gatersleben,Germany, AnnaM.Wobus Baltimore,MD, KennethR.Boheler May2005 ListofContents FactorsInvolvedinSelf-RenewalandPluripotency ofEmbryonicStemCells . . . . . . . . . . . . . . . . . . . . . . . . . . 1 H.Darr,N.Benvenisty EmbryonicStemCell-DerivedEmbryoidBodies:AnInVitroModel ofEutherianPregastrulationDevelopmentandEarlyGastrulation . . . 21 G.Weitzer EmbryonicStemCells:ANovelToolfortheStudyofAntiangiogenesis andTumor-InducedAngiogenesis . . . . . . . . . . . . . . . . . . . . . 53 M.Wartenberg,F.Dönmez,P.Budde,H.Sauer CardiacRepairbyEmbryonicStem-DerivedCells . . . . . . . . . . . . 73 M.Rubart,L.J.Field CardiomyocytesfromHumanEmbryonicStemCells . . . . . . . . . . 101 R.Passier,C.Denning,C.Mummery AutocrineandIntracrineSignalingforCardiogenesisinEmbryonicStem Cells:ACluefortheDevelopmentofNovelDifferentiatingAgents . . . 123 C.Ventura,A.Branzi TherapeuticPotentialofStemCellsinDiabetes . . . . . . . . . . . . . 147 E.Roche,R.Enseñat-Waser,J.A.Reig,J.Jones,T.León-Quinto,B.Soria TheStemCellContinuum:ANewModelofStemCellRegulation . . . . 169 P.J.Quesenberry,G.A.Colvin,M.S.Dooner MarkersofAdultTissue-BasedStemCells . . . . . . . . . . . . . . . . 185 M.R.Alison,M.Brittan,M.J.Lovell,N.A.Wright DesignerCytokinesforHumanHaematopoieticProgenitorCell Expansion:ImpactforTissueRegeneration . . . . . . . . . . . . . . . . 229 S.Rose-John X ListofContents MesenchymalStemCells:Isolation,InVitroExpansion andCharacterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249 N.BeyerNardi,L.daSilvaMeirelles NeovascularizationandCardiacRepairbyBoneMarrow-DerivedStem Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283 C.Badorff,S.Dimmeler ThePotentialUseofMyogenicStemCellsinRegenerativeMedicine . . 299 G.Grenier,M.A.Rudnicki NeuralStemCells:OnWhereTheyHide,inWhichDisguise,andHow WeMayLureThemOut . . . . . . . . . . . . . . . . . . . . . . . . . . 319 B.Berninger,M.A.Hack,M.Götz CellTransplantationforPatientswithParkinson’sDisease . . . . . . . . 361 G.Paul PostmodernBiology:(Adult)(Stem)CellsArePlastic,Stochastic,Com- plex,andUncertain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389 N.D.Theise,R.Harris SubjectIndex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409 ListofContributors Addressesgivenatthebeginningofrespectivechapters Alison,M.R. 185 León-Quinto,T. 147 Lovell,M. 185 Badorff,C. 283 Benvenisty,N. 1 Mummery,C. 101 Berninger,B. 319 BeyerNardi,N. 249 Passier,R. 101 Branzi,A. 123 Paul,G. 361 Brittan,M. 185 Budde,P. 53 Quesenberry,P.J. 169 Colvin,G.A. 169 Reig,J.A. 147 Roche,E. 147 Darr,H. 1 Rose-John,S. 229 Denning,C. 101 Rubart,M. 73 Dimmeler,S. 283 Rudnicki,M.A. 299 Dönmez,F. 53 Dooner,M.S. 169 Sauer,H. 53 Enseñat-Waser,R. 147 SilvaMeirelles,L.da 249 Soria,B. 147 Field,L.J. 73 Theise,N.D. 389 Götz,M. 319 Grenier,G. 299 Ventura,C. 123 Hack,M. 319 Wartenberg,M. 53 Harris,R. 389 Weitzer,G. 21 Jones,J. 147 Wright,N.A. 185
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