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: 1/4441 l- ^( s, |; Q. l
4 |  R( W. M+ M2 L, H

1 G+ X/ h1 `! g* U0 m+ P3 ]+ r+ }) ~- O4 e" v
8 l; j( @8 k# O) q! W/ v1 U
Inafindingthatmayopenanewavenuetotreatingdiabetes,researchersshowthatcellsfromthebonemarrowgiverisetoinsulin-producingcellsinthepancreasofmice.Thesemorphedcellsactuallyproducethehormoneinsulininresponsetoglucoseanddisplayothercharacteristicsdemonstratingthattheytrulyfunctionaspancreascells,accordingtoanewstudybyresearchersfromNYUSchoolofMedicine.! [3 y: a; j, I( s) b
ThestudyispublishedintheMarch14issueoftheJournalofClinicalInvestigation.Theresearcherscautionthatthefindingscannotbeappliedtotreatingdiabeticsnow,butmayonedayprovideameanstoproduceunlimitedquantitiesoffunctionalinsulin-producingcellsculledfromthebonemarrowofdiabetespatients.Sincepatientswouldproducetheirowncellsfortransplantation,itispossiblethatthecellswouldnotberejectedbytheirimmunesystem.+ T( T1 V1 l& h
Clearlymuchworkremainstobedone,saysMehboobA.Hussain,M.D.,AssistantProfessorofMedicineandPharmacology,wholedthestudy.ButIamabsolutelyexcitedbythepotentialapplicationsofourfindings,hesays.Inourbody,thereisanadditional,easilyaccessiblesourceofcellsthatarecapableofbecominginsulin-producingpancreaticendocrinecells.Transplantationofbonemarrowstemcellsalreadyisaroutineprocedurefortreatingcancerandotherdiseases,andwecouldbuildonthatexperience.
! D: \2 Z, G% F7 J: N; J0 [Dr.Hussain'sstudyisdescribedaselegantinanaccompanyingeditorialbyDrs.VivianLeeandMarkusStoffel,twodiabetesresearchersfromTheRockefellerUniversity,publishedinthesameissueofthejournal.Dr.HussainusedamolecularbiologytechniquecalledCRE-loxPthatallowedhimtoidentifyandisolatebonemarrowderivedcellsandtostudythemmorecloselythanhadpreviouslybeenpossible.9 K. G6 [/ ]" T( K% x
Oneofthelongstandinggoalsofdiabetesresearchistofindawaytoreplacetheinsulin-producingcellsinthepancreasthataredamagedordestroyedinsomeformsofdiabetes.ThesecellsarecalledbetacellsandtheyarefoundincellgroupscalledisletsofLangerhansinthepancreas.Inrecentyearsdoctorshavereportedthattheysuccessfullytransplantedpancreaticisletsfromcadaversintosomeseverelyilldiabetics,mostofwhomweresubsequentlyfreedfromdailyinsulinshots.Insulinregulatesbloodsugarlevels.Immunosuppressivedrugswererequiredtopreventrejectionofthetransplants.
- M: `4 l- E$ S/ ?1 d$ xHowever,thesupplyofisletsfromcadaversisextremelylimited,somedicalresearchersarelookingelsewhere.Severalresearchgroupshavereportedthatembryonicstemcellsandcellsfoundinthepancreas(otherthanbetacells)couldbeconvertedintoinsulin-producingcells,butuntilnownoonehadspecificallyexploredthebonemarrowasasourceofbetacells.(Thebonemarrownormallyreplenishesbloodcellsandinrecentyearsresearchershaveshownthatstemcellsfromthemarrowcanbecomecellsofotherorgans.)
. _+ ]5 Z2 X' E1 ~! ^5 d' q  C8 _TheCRE-loxPsystemisasortofDNAeditingtechniquethatmolecularbiologistswidelyemploytoengineergenes.Inthenewstudy,Dr.Hussainusedthesystemtoingeniouslycreatemalemicewithbonemarrowcellsthatproduceaproteincalledenhancedgreenfluorescentprotein(EGFP)onlyinthepresenceofactivatedinsulingenes,whicharetypicallyfoundinpancreaticbetacells.EGFPimpartsagreenglowtocells,whichmakesiteasytoidentifythem.Hethentransplantedthebonemarrowfromthesemalesintofemalemicewhosebonemarrowhadbeendestroyedbyradiation.
/ e: `& B; R2 {Afterfourtosixweeks,Dr.HussaindetectedasmallnumberoftheglowinggreencellsinthepancreaticisletsofLangerhansofthefemalemice.Furtheranalysisshowedthatthesecellscamefromthebonemarrowandfunctionedastheinsulin-producingbetacells.ThesecellsallcontainedtheYchromosome,whichcouldonlyhavecomefromthemaledonor.Thecellsalsosecretedinsulininresponsetoglucose,oneofthesignaturesofpancreaticbetacells,andexhibitedelectricalactivityandotherpropertiesofbetacells.
2 D% L+ o# n5 D0 I/ e" y% ^0 }3 XMoreover,asecondsetofexperimentsshowedthatthesebonemarrowderivedcellswereunlikelytobearesultofcellsfusingtogether.Someresearchershavesuggestedthattheconversionofstemcellsintodifferentiatedtissueisnotreal,butisduetoartifactsofexperimentaldesignproducedbythefusionofYchromosome-bearingcellswithhostcellsalreadypresentinthetissue.However,inthesecondsetofexperiments,Dr.HussainusedtheCRE-loxPsystemtodemonstratethattransplantedY-chromosomebonemarrowstemcellsarenotfusingwithpancreascellsinfemalerecipientmice.
0 X, }# e" y' V! S( \Despitethepromisingresults,therearecaveatstothestudy.Only1.7to3percentofbetacellsinthepancreasofthefemalemicecamefromtransformedbone-marrowstemcells,asmallnumber,anditisn'tknownwhichsubpopulationofstemcellsinthebonemarrowaretheactualsourceofinsulin-producingcells.Furthermore,itisn'tknownwhathappensindiabeticmiceafterbonemarrowtransplantation.Dr.Hussainhasproceededwithsimilarstudiesindiabeticmiceandwithexperimentsthatcouldhelpclarifyhowbonemarrowstemcellsbecomebetacellsinthepancreas." Z( ^7 q2 ]/ R% Q) T
Ourstudyisn'tthefinalproof,saysDr.Hussain.Westillneedtofindouthowwelltheseconvertedcellsarefunctioningcomparedtoindigenousbetacellsinthepancreas.Alotmoreworkneedstobedone.Nevertheless,ourstudydemonstratesthepotentialforusingthebonemarrowasasourceofinsulin-producingcells.
5 S) f: L7 V! P. c1 e  Z# f' W0 o8 l' a6 R' M* ^7 i0 B; o4 k  _
8 P  u/ e5 F$ i5 h% N; s
' q9 l( j8 h, [2 Z" k
+ U1 W: m, K: [

$ `7 Z" V4 A" u1 F# h7 N% @3 |" g作者:   p, e$ A- B; |) U8 U3 x2 @
来源: New York University Medical Center and School of Medicine
! N. i" c% f4 K, ^发布者: 刘斌