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Inafindingthatmayopenanewavenuetotreatingdiabetes,researchersshowthatcellsfromthebonemarrowgiverisetoinsulin-producingcellsinthepancreasofmice.Thesemorphedcellsactuallyproducethehormoneinsulininresponsetoglucoseanddisplayothercharacteristicsdemonstratingthattheytrulyfunctionaspancreascells,accordingtoanewstudybyresearchersfromNYUSchoolofMedicine. : u* U4 u5 d0 OThestudyispublishedintheMarch14issueoftheJournalofClinicalInvestigation.Theresearcherscautionthatthefindingscannotbeappliedtotreatingdiabeticsnow,butmayonedayprovideameanstoproduceunlimitedquantitiesoffunctionalinsulin-producingcellsculledfromthebonemarrowofdiabetespatients.Sincepatientswouldproducetheirowncellsfortransplantation,itispossiblethatthecellswouldnotberejectedbytheirimmunesystem. ! U" R' L) Q5 ^$ t5 uClearlymuchworkremainstobedone,saysMehboobA.Hussain,M.D.,AssistantProfessorofMedicineandPharmacology,wholedthestudy.ButIamabsolutelyexcitedbythepotentialapplicationsofourfindings,hesays.Inourbody,thereisanadditional,easilyaccessiblesourceofcellsthatarecapableofbecominginsulin-producingpancreaticendocrinecells.Transplantationofbonemarrowstemcellsalreadyisaroutineprocedurefortreatingcancerandotherdiseases,andwecouldbuildonthatexperience., A; z7 _' i+ U
Dr.Hussain'sstudyisdescribedaselegantinanaccompanyingeditorialbyDrs.VivianLeeandMarkusStoffel,twodiabetesresearchersfromTheRockefellerUniversity,publishedinthesameissueofthejournal.Dr.HussainusedamolecularbiologytechniquecalledCRE-loxPthatallowedhimtoidentifyandisolatebonemarrowderivedcellsandtostudythemmorecloselythanhadpreviouslybeenpossible. & a5 L% g6 s) A) QOneofthelongstandinggoalsofdiabetesresearchistofindawaytoreplacetheinsulin-producingcellsinthepancreasthataredamagedordestroyedinsomeformsofdiabetes.ThesecellsarecalledbetacellsandtheyarefoundincellgroupscalledisletsofLangerhansinthepancreas.Inrecentyearsdoctorshavereportedthattheysuccessfullytransplantedpancreaticisletsfromcadaversintosomeseverelyilldiabetics,mostofwhomweresubsequentlyfreedfromdailyinsulinshots.Insulinregulatesbloodsugarlevels.Immunosuppressivedrugswererequiredtopreventrejectionofthetransplants.9 R. O' i$ Y9 ~2 ]2 `! `1 l: p) T3 G; k
However,thesupplyofisletsfromcadaversisextremelylimited,somedicalresearchersarelookingelsewhere.Severalresearchgroupshavereportedthatembryonicstemcellsandcellsfoundinthepancreas(otherthanbetacells)couldbeconvertedintoinsulin-producingcells,butuntilnownoonehadspecificallyexploredthebonemarrowasasourceofbetacells.(Thebonemarrownormallyreplenishesbloodcellsandinrecentyearsresearchershaveshownthatstemcellsfromthemarrowcanbecomecellsofotherorgans.) ) f4 H0 j" h5 O9 A4 jTheCRE-loxPsystemisasortofDNAeditingtechniquethatmolecularbiologistswidelyemploytoengineergenes.Inthenewstudy,Dr.Hussainusedthesystemtoingeniouslycreatemalemicewithbonemarrowcellsthatproduceaproteincalledenhancedgreenfluorescentprotein(EGFP)onlyinthepresenceofactivatedinsulingenes,whicharetypicallyfoundinpancreaticbetacells.EGFPimpartsagreenglowtocells,whichmakesiteasytoidentifythem.Hethentransplantedthebonemarrowfromthesemalesintofemalemicewhosebonemarrowhadbeendestroyedbyradiation.& r- {2 o( M4 u1 M; j$ Z
Afterfourtosixweeks,Dr.HussaindetectedasmallnumberoftheglowinggreencellsinthepancreaticisletsofLangerhansofthefemalemice.Furtheranalysisshowedthatthesecellscamefromthebonemarrowandfunctionedastheinsulin-producingbetacells.ThesecellsallcontainedtheYchromosome,whichcouldonlyhavecomefromthemaledonor.Thecellsalsosecretedinsulininresponsetoglucose,oneofthesignaturesofpancreaticbetacells,andexhibitedelectricalactivityandotherpropertiesofbetacells. 3 N2 R; t0 i2 g8 t+ V/ n3 rMoreover,asecondsetofexperimentsshowedthatthesebonemarrowderivedcellswereunlikelytobearesultofcellsfusingtogether.Someresearchershavesuggestedthattheconversionofstemcellsintodifferentiatedtissueisnotreal,butisduetoartifactsofexperimentaldesignproducedbythefusionofYchromosome-bearingcellswithhostcellsalreadypresentinthetissue.However,inthesecondsetofexperiments,Dr.HussainusedtheCRE-loxPsystemtodemonstratethattransplantedY-chromosomebonemarrowstemcellsarenotfusingwithpancreascellsinfemalerecipientmice. : L: l U% e" m$ e; C5 lDespitethepromisingresults,therearecaveatstothestudy.Only1.7to3percentofbetacellsinthepancreasofthefemalemicecamefromtransformedbone-marrowstemcells,asmallnumber,anditisn'tknownwhichsubpopulationofstemcellsinthebonemarrowaretheactualsourceofinsulin-producingcells.Furthermore,itisn'tknownwhathappensindiabeticmiceafterbonemarrowtransplantation.Dr.Hussainhasproceededwithsimilarstudiesindiabeticmiceandwithexperimentsthatcouldhelpclarifyhowbonemarrowstemcellsbecomebetacellsinthepancreas.1 s: m6 j. z% b" Q0 S: C7 v
Ourstudyisn'tthefinalproof,saysDr.Hussain.Westillneedtofindouthowwelltheseconvertedcellsarefunctioningcomparedtoindigenousbetacellsinthepancreas.Alotmoreworkneedstobedone.Nevertheless,ourstudydemonstratesthepotentialforusingthebonemarrowasasourceofinsulin-producingcells.% G. T' K, Q6 R( g) T+ [3 z* B
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来源: New York University Medical Center and School of Medicine / d* c; B. t; X e# v/ j# x) w发布者: 刘斌