Bone marrow transplantation as method of treatment of mdx mice myodystrophy

Cellular Therapy and Transplantation

Violeta V. Kravtsova¹  Natalie A. Timonina¹  Anastasia V. Sokolova¹  Igor I. Krivoy¹  Viacheslav M. Mikhailov¹ 

关键词:  monogenic myodystrophy;    mdx mice;    bone marrow transplantation;   

DOI  :  10.3205/ctt-2011-No12-abstract22

学科分类：肿瘤学

来源: Universitaetsklinikum Hamburg - Eppendorf / University Medical Center Hamburg - Eppendorf

【 摘 要 】

Inthecourseofmonogenicdiseasesstemcellscontainmutantgenes,which,whenexpressedindifferentiatedcells,causethedisturbanceofthecell’sfunctionandsurvival.Thereplacementofthemutantstemcellswithwildstemcellsisseenasradicalapproachtothetreatmentofmonogenicdiseases.Bonemarrowtransplantationsareusedtotreatmonogenicdiseasesβ-thalassemiaandsicklecellanemia.Wepresenttheresultsoftreatmentofthemonogenicdiseasemyodystrophyofmdxmice,thecounterpartofhumanDuchennemyodystrophy,byC57BL/6bonemarrowtransplantation.After3,5,and7.5GyX-rayirradiation,mdxmiceweretransplantedwithsyngeneicC57BL/6micebonemarrow.Skeletalmusclefibers(MF)anddiaphragmmusclefiberswerestudiedforMFdeath,accumulationofMFwithoutcentralnuclei,andfordystrophinsynthesis.Synapseswereanalyzedbyconfocalmicroscopyafterstainingwithα-Bungarothoxin–tetramethyl-rhodamine.Themembranerestingpotentialofterminalplates(MRP)wasmeasuredbythemicroelectrodetechnique.Afterirradiationwith5and7.5Gy,bonemarrowtransplantationwasnotaccompaniedbyagrowthofdystrophinsynthesisandbyincreasingofdifferentiationlevel.After3Gyirradiationtherewasgrowthofdystrophin-positiveMFfrom1.1%(beforetransplantation)upto4.1%(2months),12.4%(4months)and27.6%(6monthsafterbonemarrowtransplantation).DiaphragmMFsweredystrophin-positiveat44%.ThelevelofMFdifferentiationincreased,MRPgrewupfrom-75.1мVuptolevelofnormalC57BL/6mice-80.7мV.ThereforethetransplantationofwildtypeofbonemarrowrestoresdifferentiationandelectrogenesisofmdxmiceskeletalMFsuptothelevelofnormalanimals.WorkwassupportedbyRFBRGrant#10-04-00970аandbyRFMEScontract№02.740.11.0094.

【 授权许可】

Unknown