文献检索作业3生物技术112 邹炜球 11114040235.docx

文献检索作业3生物技术112 邹炜球 11114040235.docx

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文献检索作业3生物技术112邹炜球11114040235

生物技术11-2邹炜球11114040235

检索主题：

人类胚胎干细胞的新潜力

一、我感兴趣的原因：

由于以下几个原因，胚胎干细胞的研究使人感到激动。

首先是它们拥有类似胚胎的全能分化性，可以从单个的受精卵发育成完整的个体，能够给我们解释完整的发育体系，而成体个体来源的多能干细胞就不可能。

同时，极早期的胚胎发育均可追溯到ES细胞，而不可能是成熟个体来源的多能干细胞。

ES细胞也是唯一不死的细胞，能够非限定地分化，是细胞的源头。

ES细胞天生就是全能的，这就是问题的关键，换言之，他们能制造机体需要的全部细胞。

最后，ES细胞是遗传操作的最早期细胞。

因此，尽管争论集中在治疗方面，但也许ES细胞最伟大的用途是作为科学研究的工具。

人胚胎干细胞的分离及体外培养的成功，将给人类带来医学革命。

如果科学家最终能够成功诱导和调控体外培养的胚胎干细胞正常的分化，这一技术将对基础研究和临床应用产生巨大的影响，有可能在以下领域发挥作用：

体外研究人胚胎的发生发育，非正常发育（通过改变细胞系的靶基因），新人类基因的发现，药物筛选和致畸实验，以及作为组织移植、细胞治疗和基因治疗的细胞源等。

人胚胎干细胞提供了在细胞和分子水平上研究人体发育过程中的极早期事件的良好材料和方法，这种研究不会引起与胚胎实验相关的伦理问题。

采用基因芯片等技术，比较胚胎干细胞以及不同发育阶段的干细胞和分化细胞的基因转录和表达，可以确定胚胎发育及细胞分化的分子机制，发现新的人类基因。

结合基因打靶技术，可发现不同基因在生命活动中的功能等。

另一个令人兴奋的应用在于新药的发现及筛选。

胚胎干细胞提供了新药的药理、药效、毒理及药代等研究的细胞水平的研究手段，大大减少了药物实验所需动物的数量。

上述实验使用的细胞系或来自其他种属的细胞系，很多时候并不能真正代表正常的人体细胞对药物的反应。

胚胎干细胞还可用来研究人类疾病的发生机制和发展过程，以便找到有效和持久的治疗方法。

二、检索方法：

打开http:

//www.sciencemag.org/

进入science网站在检索栏输入AllsciencejournalsEmbryonicstemcellresearchandapplication搜索结果：

1、NewPotentialforHumanEmbryonicStemCells

下图为检索文献结果：

原文：

Science6November1998:

Vol.282no.5391pp.1061-1062

DOI:

10.1126/science.282.5391.1061

Perspective

CELLBIOLOGY

NewPotentialforHumanEmbryonicStemCells

1.JohnGearhart*

+AuthorAffiliations

1.TheauthorisintheDepartmentofGynecologyandObstetrics,JohnsHopkinsMedicine,Baltimore,MD21287,USA.E-mail:

gearhart@jhmi.edu

Pluripotentialstemcells,presentintheearlystagesofembryodevelopment,cangenerateallofthecelltypesinafetusandintheadultandarecapableofself-renewal.Arenewable,tissueculturesourceofhumancellscapableofdifferentiatingintoawidevarietyofcelltypeswouldhavebroadapplicationsinbasicresearchandtransplantationtherapies.Amajorstepinrealizingthisgoalhasnowbeentakenwiththedemonstrationthathumanembryonicstemcellscanbegrowninculture.Thesestemcellshavebeenderivedinculturefromtwoembryonictissues:

innercellmassesofblastocysts（thosecellswithintheconceptusthatformtheembryoproper）andprimordialgermcells.Embryonicstem（ES）cellswerefirstderivedfromtheinnercellmassesofmouseblastocystsintheearly1980s（1,2）.Morerecently,primordialgermcellcultureswerefoundtogiverisetocellswithcharacteristicsofEScellsandweredesignatedEG（embryonicgerm）todistinguishtheirtissueoforigin（3,4）.ESandEGcellshavenowbeenderivedfromembryosofothermammals,includingprimates（5–10）.Nowonpage1145ofthisissue,Thomsonetal.（11）reportthederivationofEScelllinesfromhumanblastocysts.

Pluripotentialstemcells,primarilyEScells,havebeenusedextensivelyinstudiesofembryogenesis,genefunction,anddevelopmentinthemouse（11）.ESandEGcellstransferredtoamouseblastocystcancontributesubstantiallytoalldifferentiatedcelltypesinthefetus,includingthegermline.Consequently,genetargetingwithinEScellshasenabledbothwhole-animalstudiesofgenefunctionandtheproductionofmousemodelsofhumangeneticdiseasesandabnormalities.ESandEGcellshavealsobeenusedtostudythedifferentiationofvariouscelltypesandtissuesinvitro,suchasneuralcells（12–16）,hematopoieticlineages（17–19）,andcardiomyocytes（20）.ES-derivedcellshavebeensuccessfullytransplantedintofetalandadultmice,wheretheyhavedemonstratedmorphologicalandfunctionalintegration（19–23）.

Thomson'sgroupattheWisconsinRegionalPrimateResearchCenterinMadison,incollaborationwiththeDepartmentsofObstetricsandGynecologyattheRambamMedicalCenterinHaifa,Israel,andtheUniversityofWisconsin,reportsthederivationoffiveindependentcelllinesfromtheinnercellmassesof14blastocysts（11）.TheEScelllineswerecontinuouslyculturedfor5to6monthsandexpressedhighlevelsoftelomeraseactivity,characteristicofcellswithhighreplicativelife-span.Thecelllineshadnormalkaryotypes（twomaleandthreefemale）andexpressedcellsurfacemarkerscharacteristicofEScells.Fourcelllinestestedproducedteratomaswhengrowninimmunocompromisedmice.Histologyofthetumorsrevealeddifferentiatedcellsderivedfromallthreeembryonicgermlayers（ectoderm,mesoderm,anddefinitiveendoderm）—aresultconsistentwithpluripotency.

ThisreportofthederivationofEScellsfromhumanblastocystsrepresentsamajortechnicalachievementwithgreatimportanceforhumanbiology.AlthoughEScellshavebeenderivedfromseveralmammalianspecies,otherspecieshaveprovedrefractoryinyieldingEScells.Itwas,therefore,notaforegoneconclusionthatEScellscouldbederivedfromhumanembryos.EarlierpublicationsfromtheThomsongroupreportingthederivationofEScellsfromnonhumanprimatesincreasedtheexpectationthatsuchcellscouldbederivedfromhumanblastocysts.Inarelatedreport,itnowappearsthathumanembryosarealsoamenabletoEGcellderivationfromprimordialgermcells（24）.

ThederivationofhumanEScellsnowraisesawholenewsetofexpectations.OnthebasisoftheuseandstudyofmouseEScells,theresearchandclinicalpotentialforhumanEScellsisenormous.Theywillbeimportantforinvitrostudiesofnormalhumanembryogenesis,abnormaldevelopment（throughthegenerationofcelllineswithtargetedgenealterationsandengineeredchromosomes）,humangenediscovery,anddrugandteratogentestingandasarenewablesourceofcellsfortissuetransplantation,cellreplacement,andgenetherapies.Theselatterapplicationscouldeventuallyprecludethedirectuseoffetaltissueintransplantationtherapies.

ItisexcitingtospeculateonhowhumanESlinescouldbeusedintissuetransplantationtherapies（seefigure）（25）.Obviousclinicaltargetswouldincludeneurodegenerativedisorders,diabetes,spinalcordinjury,andhematopoieticrepopulation.Inadditiontopossiblyprovidinglargenumbersofpurepopulationsofcellsfortransplantation,EScellswouldalsolendthemselvestoseveralstrategiesforthepreventionofimmunologicaltissuerejectionaftertransplantation,including（i）bankingofmultipleEScelllinesrepresentingaspectrumofmajorhistocompatibilitycomplex（MHC）allelestoserveasasourceforMHCmatching;（ii）creationofuniversaldonorlines,inwhichtheMHCgenescouldbegeneticallyalteredsorejectionwouldnotoccur,anapproachthathasbeentriedwithmoderatesuccessinthemouse;（iii）customizationofEScellsthroughtransgenesisandgenetargetingsothatapotentialrecipient'sMHCgenesareintroducedintoEScellsthroughhomologousrecombination;and（iv）productionofESlinescontainingthegenomeoftheprospectiverecipient.BlastocystsobtainedthroughnucleartransferswouldbeusedtogenerateEScells,whichthencouldbedifferentiatedtospecificlineagesfortransfertothenucleardonor（26）.BecauseEGcellshavebeenshowntoreprogramadultnuclei（27）aftercellhybridformation,itmayeventuallybepossibletodonucleartransfersintopluripotentstemcells,whichcouldthenbeexpandedanddifferentiated.

Embryonicstemcelldifferentiation.

PossibleapplicationsofEScellstotransplantationtherapy.

Torealizethefullpotentialofhumanpluripotentstemcells,challengingresearchliesaheadandseveralpracticalissuesmustberesolved.TheconditionsnecessarytoderivehumanEScellsefficientlyandreliablymustbedefined.HowdidtheThomsongroupsucceedwhen,onthesurface,theirprotocolissosimilartothatofotherinvestigators?

TheirpreviousexperiencewithnonhumanprimateEScellderivationwascertainlycriticalforthissuccess.Thomsonetal.（11）reportthatof14innercellmassesplacedinculture,fiveEScelllineswereestablished.Thisresultisexcellent,butcoulditbebetter?

AretherewaysofassayingblastocystsfortheirpotentialofyieldingEScells?

Asinthemouse,aretherepredisposinggenesforthisproperty?

Arethereotherextrinsicorintrinsicfactorsthatmayleadtoagreatersuccessrate?

Theconditionsfordirected,lineage-restricteddifferentiationofEScellsmustbedefined.StudiestodateonEScelldifferentiationinvitrorelyprimarilyontheselectionandenrichmentofspecificlineagesfromthemanythatmaybepresentwhencelldifferentiationisinduced.Also,strategiesmustbedevelopedtoobtainthelargenumbersofpurepopulationsofcellsthatwouldberequiredforengraftments.Intheshortterm,feedercell-independentlineswillhavetobederivedandmethodsforcompletecelldisaggregationdeveloped.Itmustalsobedeterminedifthecellsareamenabletotransfections,enablingselectionandgene-targetingstrategies.

Reportsontheisolationofhumanpluripotentstemcellswillnodoubtcatchthepubliceye,andtherewillbeexpressionsofconcern,rekindlingthedebateonhumanembryoresearch.Thedebatewillencompassthesourceofthecells,humancloningpotential,andthepossibilitiesofgermlinemodifications.Fouryearsago,theHumanEmbryoResearchPanel'sreporttothedirectoroftheNationalInstitutesofHealth（NIH）concludedthatresearchderivingEScellsisacceptableaslongasembryosarenotcreatedexpresslyforresearchpurposes.Severalissueswillhavetoberesolvedtopermittheappropriateexploitationoftheuniquenessandpotentialofthesecells.Currently,asbroadlywritten,U.S.federallawbanstheuseoffederalfundsforthederivationofthesecells[PublicLaw105–78,Section513（a）].Todate,researchinthisareahasbeensponsoredthroughprivateandcorporatefunding,withhospitalandacademicinstitutionalinternalreviewboardapprovalandinformedpatientconsent.ItisnotclearwhetherNIHfundingnecessarytorealizethebiomedicalpotentialofthecellswillbeavailabletosupportstudi