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: 1/444# t' @$ e, w4 a; O1 X
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Inafindingthatmayopenanewavenuetotreatingdiabetes,researchersshowthatcellsfromthebonemarrowgiverisetoinsulin-producingcellsinthepancreasofmice.Thesemorphedcellsactuallyproducethehormoneinsulininresponsetoglucoseanddisplayothercharacteristicsdemonstratingthattheytrulyfunctionaspancreascells,accordingtoanewstudybyresearchersfromNYUSchoolofMedicine.& D5 E, W  U1 L
ThestudyispublishedintheMarch14issueoftheJournalofClinicalInvestigation.Theresearcherscautionthatthefindingscannotbeappliedtotreatingdiabeticsnow,butmayonedayprovideameanstoproduceunlimitedquantitiesoffunctionalinsulin-producingcellsculledfromthebonemarrowofdiabetespatients.Sincepatientswouldproducetheirowncellsfortransplantation,itispossiblethatthecellswouldnotberejectedbytheirimmunesystem.
- X% x( E5 B0 jClearlymuchworkremainstobedone,saysMehboobA.Hussain,M.D.,AssistantProfessorofMedicineandPharmacology,wholedthestudy.ButIamabsolutelyexcitedbythepotentialapplicationsofourfindings,hesays.Inourbody,thereisanadditional,easilyaccessiblesourceofcellsthatarecapableofbecominginsulin-producingpancreaticendocrinecells.Transplantationofbonemarrowstemcellsalreadyisaroutineprocedurefortreatingcancerandotherdiseases,andwecouldbuildonthatexperience.
6 B0 G1 q+ c# ^5 ~  _5 qDr.Hussain'sstudyisdescribedaselegantinanaccompanyingeditorialbyDrs.VivianLeeandMarkusStoffel,twodiabetesresearchersfromTheRockefellerUniversity,publishedinthesameissueofthejournal.Dr.HussainusedamolecularbiologytechniquecalledCRE-loxPthatallowedhimtoidentifyandisolatebonemarrowderivedcellsandtostudythemmorecloselythanhadpreviouslybeenpossible.
3 |* n% A' ?; J' Z+ T8 n9 ^Oneofthelongstandinggoalsofdiabetesresearchistofindawaytoreplacetheinsulin-producingcellsinthepancreasthataredamagedordestroyedinsomeformsofdiabetes.ThesecellsarecalledbetacellsandtheyarefoundincellgroupscalledisletsofLangerhansinthepancreas.Inrecentyearsdoctorshavereportedthattheysuccessfullytransplantedpancreaticisletsfromcadaversintosomeseverelyilldiabetics,mostofwhomweresubsequentlyfreedfromdailyinsulinshots.Insulinregulatesbloodsugarlevels.Immunosuppressivedrugswererequiredtopreventrejectionofthetransplants.
% i* a( r- K: s) aHowever,thesupplyofisletsfromcadaversisextremelylimited,somedicalresearchersarelookingelsewhere.Severalresearchgroupshavereportedthatembryonicstemcellsandcellsfoundinthepancreas(otherthanbetacells)couldbeconvertedintoinsulin-producingcells,butuntilnownoonehadspecificallyexploredthebonemarrowasasourceofbetacells.(Thebonemarrownormallyreplenishesbloodcellsandinrecentyearsresearchershaveshownthatstemcellsfromthemarrowcanbecomecellsofotherorgans.)$ r% m: l0 ~# F' V5 j& c4 A/ J0 P) W
TheCRE-loxPsystemisasortofDNAeditingtechniquethatmolecularbiologistswidelyemploytoengineergenes.Inthenewstudy,Dr.Hussainusedthesystemtoingeniouslycreatemalemicewithbonemarrowcellsthatproduceaproteincalledenhancedgreenfluorescentprotein(EGFP)onlyinthepresenceofactivatedinsulingenes,whicharetypicallyfoundinpancreaticbetacells.EGFPimpartsagreenglowtocells,whichmakesiteasytoidentifythem.Hethentransplantedthebonemarrowfromthesemalesintofemalemicewhosebonemarrowhadbeendestroyedbyradiation.; {* N4 ^1 y1 m+ q; Y
Afterfourtosixweeks,Dr.HussaindetectedasmallnumberoftheglowinggreencellsinthepancreaticisletsofLangerhansofthefemalemice.Furtheranalysisshowedthatthesecellscamefromthebonemarrowandfunctionedastheinsulin-producingbetacells.ThesecellsallcontainedtheYchromosome,whichcouldonlyhavecomefromthemaledonor.Thecellsalsosecretedinsulininresponsetoglucose,oneofthesignaturesofpancreaticbetacells,andexhibitedelectricalactivityandotherpropertiesofbetacells.: }7 g$ b2 ?+ L, O6 D' X. A
Moreover,asecondsetofexperimentsshowedthatthesebonemarrowderivedcellswereunlikelytobearesultofcellsfusingtogether.Someresearchershavesuggestedthattheconversionofstemcellsintodifferentiatedtissueisnotreal,butisduetoartifactsofexperimentaldesignproducedbythefusionofYchromosome-bearingcellswithhostcellsalreadypresentinthetissue.However,inthesecondsetofexperiments,Dr.HussainusedtheCRE-loxPsystemtodemonstratethattransplantedY-chromosomebonemarrowstemcellsarenotfusingwithpancreascellsinfemalerecipientmice.' \: @7 J3 J" O2 T/ G1 a/ u
Despitethepromisingresults,therearecaveatstothestudy.Only1.7to3percentofbetacellsinthepancreasofthefemalemicecamefromtransformedbone-marrowstemcells,asmallnumber,anditisn'tknownwhichsubpopulationofstemcellsinthebonemarrowaretheactualsourceofinsulin-producingcells.Furthermore,itisn'tknownwhathappensindiabeticmiceafterbonemarrowtransplantation.Dr.Hussainhasproceededwithsimilarstudiesindiabeticmiceandwithexperimentsthatcouldhelpclarifyhowbonemarrowstemcellsbecomebetacellsinthepancreas.$ O* t7 ^' q8 z6 n5 V& i. @
Ourstudyisn'tthefinalproof,saysDr.Hussain.Westillneedtofindouthowwelltheseconvertedcellsarefunctioningcomparedtoindigenousbetacellsinthepancreas.Alotmoreworkneedstobedone.Nevertheless,ourstudydemonstratesthepotentialforusingthebonemarrowasasourceofinsulin-producingcells.5 u, n$ z( B, T/ c
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来源: New York University Medical Center and School of Medicine
& o$ c9 s! h3 L. }+ `3 R6 w( i发布者: 刘斌