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! {" |2 b: v# t8 l7 a2 ^5 a
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Inafindingthatmayopenanewavenuetotreatingdiabetes,researchersshowthatcellsfromthebonemarrowgiverisetoinsulin-producingcellsinthepancreasofmice.Thesemorphedcellsactuallyproducethehormoneinsulininresponsetoglucoseanddisplayothercharacteristicsdemonstratingthattheytrulyfunctionaspancreascells,accordingtoanewstudybyresearchersfromNYUSchoolofMedicine.0 o- h. O& m& ^9 F3 Q. y. [8 T
ThestudyispublishedintheMarch14issueoftheJournalofClinicalInvestigation.Theresearcherscautionthatthefindingscannotbeappliedtotreatingdiabeticsnow,butmayonedayprovideameanstoproduceunlimitedquantitiesoffunctionalinsulin-producingcellsculledfromthebonemarrowofdiabetespatients.Sincepatientswouldproducetheirowncellsfortransplantation,itispossiblethatthecellswouldnotberejectedbytheirimmunesystem.3 Y4 c' K) O5 b
Clearlymuchworkremainstobedone,saysMehboobA.Hussain,M.D.,AssistantProfessorofMedicineandPharmacology,wholedthestudy.ButIamabsolutelyexcitedbythepotentialapplicationsofourfindings,hesays.Inourbody,thereisanadditional,easilyaccessiblesourceofcellsthatarecapableofbecominginsulin-producingpancreaticendocrinecells.Transplantationofbonemarrowstemcellsalreadyisaroutineprocedurefortreatingcancerandotherdiseases,andwecouldbuildonthatexperience.
& e4 |( k5 `6 ^, O( x# YDr.Hussain'sstudyisdescribedaselegantinanaccompanyingeditorialbyDrs.VivianLeeandMarkusStoffel,twodiabetesresearchersfromTheRockefellerUniversity,publishedinthesameissueofthejournal.Dr.HussainusedamolecularbiologytechniquecalledCRE-loxPthatallowedhimtoidentifyandisolatebonemarrowderivedcellsandtostudythemmorecloselythanhadpreviouslybeenpossible.
0 F' j- }8 B$ |; f. S- ~7 iOneofthelongstandinggoalsofdiabetesresearchistofindawaytoreplacetheinsulin-producingcellsinthepancreasthataredamagedordestroyedinsomeformsofdiabetes.ThesecellsarecalledbetacellsandtheyarefoundincellgroupscalledisletsofLangerhansinthepancreas.Inrecentyearsdoctorshavereportedthattheysuccessfullytransplantedpancreaticisletsfromcadaversintosomeseverelyilldiabetics,mostofwhomweresubsequentlyfreedfromdailyinsulinshots.Insulinregulatesbloodsugarlevels.Immunosuppressivedrugswererequiredtopreventrejectionofthetransplants.0 O0 C7 x7 j" O- W; e+ Z( @
However,thesupplyofisletsfromcadaversisextremelylimited,somedicalresearchersarelookingelsewhere.Severalresearchgroupshavereportedthatembryonicstemcellsandcellsfoundinthepancreas(otherthanbetacells)couldbeconvertedintoinsulin-producingcells,butuntilnownoonehadspecificallyexploredthebonemarrowasasourceofbetacells.(Thebonemarrownormallyreplenishesbloodcellsandinrecentyearsresearchershaveshownthatstemcellsfromthemarrowcanbecomecellsofotherorgans.)4 h0 ?+ L: _7 B' {" B; a1 |
TheCRE-loxPsystemisasortofDNAeditingtechniquethatmolecularbiologistswidelyemploytoengineergenes.Inthenewstudy,Dr.Hussainusedthesystemtoingeniouslycreatemalemicewithbonemarrowcellsthatproduceaproteincalledenhancedgreenfluorescentprotein(EGFP)onlyinthepresenceofactivatedinsulingenes,whicharetypicallyfoundinpancreaticbetacells.EGFPimpartsagreenglowtocells,whichmakesiteasytoidentifythem.Hethentransplantedthebonemarrowfromthesemalesintofemalemicewhosebonemarrowhadbeendestroyedbyradiation.
# _; i* l3 X# P& HAfterfourtosixweeks,Dr.HussaindetectedasmallnumberoftheglowinggreencellsinthepancreaticisletsofLangerhansofthefemalemice.Furtheranalysisshowedthatthesecellscamefromthebonemarrowandfunctionedastheinsulin-producingbetacells.ThesecellsallcontainedtheYchromosome,whichcouldonlyhavecomefromthemaledonor.Thecellsalsosecretedinsulininresponsetoglucose,oneofthesignaturesofpancreaticbetacells,andexhibitedelectricalactivityandotherpropertiesofbetacells.
7 G2 V3 S! {; v% g: lMoreover,asecondsetofexperimentsshowedthatthesebonemarrowderivedcellswereunlikelytobearesultofcellsfusingtogether.Someresearchershavesuggestedthattheconversionofstemcellsintodifferentiatedtissueisnotreal,butisduetoartifactsofexperimentaldesignproducedbythefusionofYchromosome-bearingcellswithhostcellsalreadypresentinthetissue.However,inthesecondsetofexperiments,Dr.HussainusedtheCRE-loxPsystemtodemonstratethattransplantedY-chromosomebonemarrowstemcellsarenotfusingwithpancreascellsinfemalerecipientmice.* d) u$ L9 A3 ?- f5 O# M
Despitethepromisingresults,therearecaveatstothestudy.Only1.7to3percentofbetacellsinthepancreasofthefemalemicecamefromtransformedbone-marrowstemcells,asmallnumber,anditisn'tknownwhichsubpopulationofstemcellsinthebonemarrowaretheactualsourceofinsulin-producingcells.Furthermore,itisn'tknownwhathappensindiabeticmiceafterbonemarrowtransplantation.Dr.Hussainhasproceededwithsimilarstudiesindiabeticmiceandwithexperimentsthatcouldhelpclarifyhowbonemarrowstemcellsbecomebetacellsinthepancreas.
+ g5 b$ B  Y: N6 w2 ZOurstudyisn'tthefinalproof,saysDr.Hussain.Westillneedtofindouthowwelltheseconvertedcellsarefunctioningcomparedtoindigenousbetacellsinthepancreas.Alotmoreworkneedstobedone.Nevertheless,ourstudydemonstratesthepotentialforusingthebonemarrowasasourceofinsulin-producingcells.
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作者: % Y" `5 U1 B/ t0 g
来源: New York University Medical Center and School of Medicine/ w, N, |/ C3 {  I$ w  a, l% p
发布者: 刘斌