1Embryonic stem cell.docx

1Embryonic stem cell.docx

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1Embryonicstemcell

Embryonicstemcell

Embryonicstemcells（EScells）arepluripotentstemcellsderivedfromtheinnercellmassoftheblastocyst,anearly-stageembryo.Humanembryosreachtheblastocyststage4–5dayspostfertilization,atwhichtimetheyconsistof50–150cells.Becauseisolatingtheembryoblastorinnercellmass（ICM）resultsinthedeathofthefertilizedhumanembryo,thisraisesethicalissues.

Whatarestemcells,andwhyaretheyimportant?

Stemcellshavetheremarkablepotentialtodevelopintomanydifferentcelltypesinthebodyduringearlylifeandgrowth.Inaddition,inmanytissuestheyserveasasortofinternalrepairsystem,dividingessentiallywithoutlimittoreplenishothercellsaslongasthepersonoranimalisstillalive.Whenastemcelldivides,eachnewcellhasthepotentialeithertoremainastemcellorbecomeanothertypeofcellwithamorespecializedfunction,suchasamusclecell,aredbloodcell,orabraincell.

Stemcellsaredistinguishedfromothercelltypesbytwoimportantcharacteristics.First,theyareunspecializedcellscapableofrenewingthemselvesthroughcelldivision,sometimesafterlongperiodsofinactivity.Second,undercertainphysiologicorexperimentalconditions,theycanbeinducedtobecometissue-ororgan-specificcellswithspecialfunctions.Insomeorgans,suchasthegutandbonemarrow,stemcellsregularlydividetorepairandreplacewornoutordamagedtissues.Inotherorgans,however,suchasthepancreasandtheheart,stemcellsonlydivideunderspecialconditions.

Untilrecently,scientistsprimarilyworkedwithtwokindsofstemcellsfromanimalsandhumans:

embryonicstemcellsandnon-embryonic"somatic"or"adult"stemcells.Thefunctionsandcharacteristicsofthesecellswillbeexplainedinthisdocument.Scientistsdiscoveredwaystoderiveembryonicstemcellsfromearlymouseembryosnearly30yearsago,in1981.Thedetailedstudyofthebiologyofmousestemcellsledtothediscovery,in1998,ofamethodtoderivestemcellsfromhumanembryosandgrowthecellsinthelaboratory.Thesecellsarecalledhumanembryonicstemcells.Theembryosusedinthesestudieswerecreatedforreproductivepurposesthroughinvitrofertilizationprocedures.Whentheywerenolongerneededforthatpurpose,theyweredonatedforresearchwiththeinformedconsentofthedonor.In2006,researchersmadeanotherbreakthroughbyidentifyingconditionsthatwouldallowsomespecializedadultcellstobe"reprogrammed"geneticallytoassumeastemcell-likestate.Thisnewtypeofstemcell,calledinducedpluripotentstemcells（iPSCs）,willbediscussedinalatersectionofthisdocument.

Stemcellsareimportantforlivingorganismsformanyreasons.Inthe3-to5-day-oldembryo,calledablastocyst,theinnercellsgiverisetotheentirebodyoftheorganism,includingallofthemanyspecializedcelltypesandorganssuchastheheart,lung,skin,sperm,eggsandothertissues.Insomeadulttissues,suchasbonemarrow,muscle,andbrain,discretepopulationsofadultstemcellsgeneratereplacementsforcellsthatarelostthroughnormalwearandtear,injury,ordisease.

Giventheiruniqueregenerativeabilities,stemcellsoffernewpotentialsfortreatingdiseasessuchasdiabetes,andheartdisease.However,muchworkremainstobedoneinthelaboratoryandtheclinictounderstandhowtousethesecellsforcell-basedtherapiestotreatdisease,whichisalsoreferredtoasregenerativeorreparativemedicine.

Laboratorystudiesofstemcellsenablescientiststolearnaboutthecells’essentialpropertiesandwhatmakesthemdifferentfromspecializedcelltypes.Scientistsarealreadyusingstemcellsinthelaboratorytoscreennewdrugsandtodevelopmodelsystemstostudynormalgrowthandidentifythecausesofbirthdefects.

Researchonstemcellscontinuestoadvanceknowledgeabouthowanorganismdevelopsfromasinglecellandhowhealthycellsreplacedamagedcellsinadultorganisms.Stemcellresearchisoneofthemostfascinatingareasofcontemporarybiology,but,aswithmanyexpandingfieldsofscientificinquiry,researchonstemcellsraisesscientificquestionsasrapidlyasitgeneratesnewdiscoveries.

1.Wheredostemcellscomefrom?

Thereareseveralsourcesofstemcells.Pluripotentstemcellscanbeisolatedfromhumanembryosthatareafewdaysold.Cellsfromtheseembryoscanbeusedtocreatepluripotentstemcell"lines"—cellculturesthatcanbegrownindefinitelyinthelaboratory.Pluripotentstemcelllineshavealsobeendevelopedfromfetaltissue（olderthan8weeksofdevelopment）.

Inlate2007,scientistsidentifiedconditionsthatwouldallowsomespecializedadulthumancellstobereprogrammedgeneticallytoassumeastemcell-likestate.Thesestemcellsarecalledinducedpluripotentstemcells（iPSCs）.IPSCsareadultcellsthathavebeengeneticallyreprogrammedtoanembryonicstemcell–likestatebybeingforcedtoexpressgenesandfactorsimportantformaintainingthedefiningpropertiesofembryonicstemcells.Althoughthesecellsmeetthedefiningcriteriaforpluripotentstemcells,itisnotknownifiPSCsandembryonicstemcellsdifferinclinicallysignificantways.MouseiPSCswerefirstreportedin2006,andhumaniPSCswerefirstreportedinlate2007.MouseiPSCsdemonstrateimportantcharacteristicsofpluripotentstemcells,includingexpressingstemcellmarkers,formingtumorscontainingcellsfromallthreegermlayers,andbeingabletocontributetomanydifferenttissueswheninjectedintomouseembryosataveryearlystageindevelopment.HumaniPSCsalsoexpressstemcellmarkersandarecapableofgeneratingcellscharacteristicofallthreegermlayers.

Althoughadditionalresearchisneeded,iPSCsarealreadyusefultoolsfordrugdevelopmentandmodelingofdiseases,andscientistshopetousethemintransplantationmedicine.Virusesarecurrentlyusedtointroducethereprogrammingfactorsintoadultcells,andthisprocessmustbecarefullycontrolledandtestedbeforethetechniquecanleadtousefultreatmentsforhumans.Inanimalstudies,thevirususedtointroducethestemcellfactorssometimescausescancers.Researchersarecurrentlyinvestigatingnon-viraldeliverystrategies.

Non-embryonic,or"adult"stemcellshavebeenidentifiedinmanyorgansandtissues.Typicallythereisaverysmallnumberofmultipotentstemcellsineachtissue,andthesecellshavealimitedcapacityforproliferation,thusmakingitdifficulttogeneratelargequantitiesofthesecellsinthelaboratory.Stemcellsarethoughttoresideinaspecificareaofeachtissue（calleda"stemcellniche"）wheretheymayremainquiescent（non-dividing）formanyyearsuntiltheyareactivatedbyanormalneedformorecells,orbydiseaseortissueinjury.Thesecellsarealsocalledsomaticstemcells.

Whyareembryonicstemcellsimportant?

Opponentsofembryonicstemcellresearchoftenarguethatembryonicstemcellresearchisnotnecessarybecauseadultstemcellsfrombonemarroworumbilicalcordbloodcellsarealreadycuringdiseases,aremorelikelytocurediseasesandthatadultstemcellswouldnotberejectedbytheimmunesystemwhentransplanted.Theyaretroubledbythecloningbecausetheyopposecreatinganembryoinordertoharvestitsstemcells.Finally,theypointoutthatcurrentmethodsofcollectingembryonicstemcellsareinefficientandcloningembryonicstemcellsmaynotbeapracticalmethodofproducingcellsfortransplantationpurposes.Theseargumentsarepartlytruebutaremisleadinganddonotjustifythecurrentrestrictionsofhumanembryonicstemcellresearch.Letusconsidersomeofthemostfrequentlycitedargumentsfororagainstadultandembryonicstemcells.

1.Areadultstemcellsalreadycuringdiseases?

Someopponentsofembryonicstemcellresearchsaythatembryonicstemcellshavenevercuredanyconditionwhileadultstemcellsarealreadycuringmanydiseases.Bonemarrowandumbilicalcordbloodstemcellshavebeenusedforovertwodecadestotreatblood-making（hematopoieticcells）disorders,suchassicklecellanemia,thalassemia,radiationorchemotherapyinducedbonemarrowdamage,andautoimmunediseases.Bonemarrowstemcelltransplantsmayaccelerateandimprovehealingfromheartattacks（myocardialinfarcts）orfailinghearts（congestiveheartfailure）.However,thereisnocredibleevidenceyetthatbonemarrowstemcellsarereplacingheartcells.Bonemarrowcellsmaybereleasingfactorsthathelpheartshealfaster.Neitherbonemarrownorumbilicalcordbloodstemcells,orothertypesofadultstemcells,havecuredneurologicalconditions,suchasbrainorspinalcordinjury,amyotrophiclateralsclerosis,multiplesclerosis,Alzheimer'sdisease,Parkinson'sdisease,ornon-neurologicaldiseasessuchasdiabetes,liverdamagefromhepatitis,andothercurrentlyincurableconditions.Wedonotknowenoughnowtopredictwhetheradultorembryonicstemcellswouldbebetterorwhichwouldbemoreeffective.Manyanimalstudieshaveshownbeneficialeffectsofembryonicstemcelltreatmentsofanimalmodelsofdiseases.Humanembryonicstemcellshavenotyetbeentransplantedintohumans.TherearenorestrictionsonadultbonemarroworumbilicalcordbloodresearchatallwhileU.S.federalgovernmentsignificantlyrestrictsfundingofhumanembryonicstemcellresearch.

2.Doadultstemcellscircumventtheproblemofimmunerejection?

Itistruethatautologousgrafts,i.e.adultstemcellstakenfromapersonandtransplantedintothesameperson,wouldnotberejectedbytheimmunesystem.However,autologousgraftscannotbeusedformanyconditions.First,autologousgraftsarenotusefulformostgenetic