骨髓干细胞可以成为胰腺细胞的来源

韩雪娜

日期: 2003-03-17 今日/总浏览: 1/4440 a! j& Y. e4 ?  ~
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Inafindingthatmayopenanewavenuetotreatingdiabetes,researchersshowthatcellsfromthebonemarrowgiverisetoinsulin-producingcellsinthepancreasofmice.Thesemorphedcellsactuallyproducethehormoneinsulininresponsetoglucoseanddisplayothercharacteristicsdemonstratingthattheytrulyfunctionaspancreascells,accordingtoanewstudybyresearchersfromNYUSchoolofMedicine.. P4 B9 X9 o7 _- j6 Z9 H8 k; C: |
ThestudyispublishedintheMarch14issueoftheJournalofClinicalInvestigation.Theresearcherscautionthatthefindingscannotbeappliedtotreatingdiabeticsnow,butmayonedayprovideameanstoproduceunlimitedquantitiesoffunctionalinsulin-producingcellsculledfromthebonemarrowofdiabetespatients.Sincepatientswouldproducetheirowncellsfortransplantation,itispossiblethatthecellswouldnotberejectedbytheirimmunesystem.
+ S) ^& O$ M( q% B7 K/ S3 LClearlymuchworkremainstobedone,saysMehboobA.Hussain,M.D.,AssistantProfessorofMedicineandPharmacology,wholedthestudy.ButIamabsolutelyexcitedbythepotentialapplicationsofourfindings,hesays.Inourbody,thereisanadditional,easilyaccessiblesourceofcellsthatarecapableofbecominginsulin-producingpancreaticendocrinecells.Transplantationofbonemarrowstemcellsalreadyisaroutineprocedurefortreatingcancerandotherdiseases,andwecouldbuildonthatexperience.
, {* e1 l! W$ E) ?Dr.Hussain'sstudyisdescribedaselegantinanaccompanyingeditorialbyDrs.VivianLeeandMarkusStoffel,twodiabetesresearchersfromTheRockefellerUniversity,publishedinthesameissueofthejournal.Dr.HussainusedamolecularbiologytechniquecalledCRE-loxPthatallowedhimtoidentifyandisolatebonemarrowderivedcellsandtostudythemmorecloselythanhadpreviouslybeenpossible.* v; C7 f& ~9 z9 n# _
Oneofthelongstandinggoalsofdiabetesresearchistofindawaytoreplacetheinsulin-producingcellsinthepancreasthataredamagedordestroyedinsomeformsofdiabetes.ThesecellsarecalledbetacellsandtheyarefoundincellgroupscalledisletsofLangerhansinthepancreas.Inrecentyearsdoctorshavereportedthattheysuccessfullytransplantedpancreaticisletsfromcadaversintosomeseverelyilldiabetics,mostofwhomweresubsequentlyfreedfromdailyinsulinshots.Insulinregulatesbloodsugarlevels.Immunosuppressivedrugswererequiredtopreventrejectionofthetransplants.( u( v/ t! v: c) ~; G- C6 y- U
However,thesupplyofisletsfromcadaversisextremelylimited,somedicalresearchersarelookingelsewhere.Severalresearchgroupshavereportedthatembryonicstemcellsandcellsfoundinthepancreas(otherthanbetacells)couldbeconvertedintoinsulin-producingcells,butuntilnownoonehadspecificallyexploredthebonemarrowasasourceofbetacells.(Thebonemarrownormallyreplenishesbloodcellsandinrecentyearsresearchershaveshownthatstemcellsfromthemarrowcanbecomecellsofotherorgans.)
' s$ C) S, U" W8 ]# c- c; pTheCRE-loxPsystemisasortofDNAeditingtechniquethatmolecularbiologistswidelyemploytoengineergenes.Inthenewstudy,Dr.Hussainusedthesystemtoingeniouslycreatemalemicewithbonemarrowcellsthatproduceaproteincalledenhancedgreenfluorescentprotein(EGFP)onlyinthepresenceofactivatedinsulingenes,whicharetypicallyfoundinpancreaticbetacells.EGFPimpartsagreenglowtocells,whichmakesiteasytoidentifythem.Hethentransplantedthebonemarrowfromthesemalesintofemalemicewhosebonemarrowhadbeendestroyedbyradiation.
! d1 [% B4 u( C& p* G  K1 HAfterfourtosixweeks,Dr.HussaindetectedasmallnumberoftheglowinggreencellsinthepancreaticisletsofLangerhansofthefemalemice.Furtheranalysisshowedthatthesecellscamefromthebonemarrowandfunctionedastheinsulin-producingbetacells.ThesecellsallcontainedtheYchromosome,whichcouldonlyhavecomefromthemaledonor.Thecellsalsosecretedinsulininresponsetoglucose,oneofthesignaturesofpancreaticbetacells,andexhibitedelectricalactivityandotherpropertiesofbetacells.5 w) j$ [. C8 D1 m: `. ~5 \* Y
Moreover,asecondsetofexperimentsshowedthatthesebonemarrowderivedcellswereunlikelytobearesultofcellsfusingtogether.Someresearchershavesuggestedthattheconversionofstemcellsintodifferentiatedtissueisnotreal,butisduetoartifactsofexperimentaldesignproducedbythefusionofYchromosome-bearingcellswithhostcellsalreadypresentinthetissue.However,inthesecondsetofexperiments,Dr.HussainusedtheCRE-loxPsystemtodemonstratethattransplantedY-chromosomebonemarrowstemcellsarenotfusingwithpancreascellsinfemalerecipientmice.
. O1 x' ?0 c/ S4 U5 ~& T4 ]( lDespitethepromisingresults,therearecaveatstothestudy.Only1.7to3percentofbetacellsinthepancreasofthefemalemicecamefromtransformedbone-marrowstemcells,asmallnumber,anditisn'tknownwhichsubpopulationofstemcellsinthebonemarrowaretheactualsourceofinsulin-producingcells.Furthermore,itisn'tknownwhathappensindiabeticmiceafterbonemarrowtransplantation.Dr.Hussainhasproceededwithsimilarstudiesindiabeticmiceandwithexperimentsthatcouldhelpclarifyhowbonemarrowstemcellsbecomebetacellsinthepancreas.
7 ]8 C3 L, o; r( @Ourstudyisn'tthefinalproof,saysDr.Hussain.Westillneedtofindouthowwelltheseconvertedcellsarefunctioningcomparedtoindigenousbetacellsinthepancreas.Alotmoreworkneedstobedone.Nevertheless,ourstudydemonstratesthepotentialforusingthebonemarrowasasourceofinsulin-producingcells.
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作者:
! L$ e" T6 k' g5 N. a; Y来源: New York University Medical Center and School of Medicine
4 k6 y7 I8 }2 s& L  x7 M发布者: 刘斌