骨髓和脐血间质干细胞联合移植治疗杜氏型进行性肌营养不良症269例疗效研究  

Effect of Combined Transplantation of Bone Marrow Mesenchymal Stem Cells and Umbilical Cord Blood Mesenchymal Stem Cells Transplantation on Muscular Dystrophy

作　　者：吕乃武[1] 杨晓凤[1] 许忆峰[1] 张轶斌[1] 王红梅[1] 吴雁翔[1] 单鸿[1] 崔激平[1] 周金旭[1] 

机构地区：[1]中国人民解放军第463医院,辽宁省沈阳市110042

出　　处：《中国全科医学》2010年第14期1525-1528,共4页Chinese General Practice

摘　　要：目的观察骨髓间质干细胞(BMSCs)和脐血间质干细胞(CMSCs)联合移植治疗杜氏型进行性肌营养不良症(DMD)的临床疗效。方法2007年6月—2009年3月对269例DMD患者行自体BMSCs和CMSCs联合移植方案进行治疗,患者均使用重组人粒细胞集落刺激因子(rhG-CSF),5～10μg/kg,2次/d,皮下注射动员骨髓干细胞4d,于第5天行骨髓采集术,局部麻醉下从髂后上棘抽取骨髓100～180ml。将采集的骨髓液经Ficoll密度梯度离心后,分离单个核细胞2.0×109,用Uitra cul Ture培养液调节细胞数量为1×105/ml～1×106/ml,接种于75mm2培养瓶中,24h换液,7～10d后收集全部细胞,总数为4.0×108/ml～1.5×109/ml。将BMSCs移植到患者四肢近端肌肉内。采集脐血80～160ml,Ficoll密度梯度离心,分离单个核细胞并诱导分化为CMSCs。将CMSC(1.0～4.8)×107细胞悬液,经静脉缓慢输注,每5～7d1次,共3次。移植后6个月对患者的肌力、步行10m和推轮椅10m所需时间、肌酸激酶水平、肌电图等进行观察。结果269例患者移植后6个月时随访,218例患者(81.0%)肌力有不同程度的增加。干细胞移植后235例患者复查心肌酶谱,其中188例(80%)患者步行10m及推轮椅10m所需时间明显缩短,与移植前比较差异有统计学意义(P<0.05),干细胞移植后患者肌酸激酶水平较移植前明显下降(P<0.01)。51例患者复查肌电图,32例(62.7%)患者波幅不同程度增高,运动单位增多,多相波减少。47例患者复查大腿肌肉磁共振成像,肌肉影像较移植前变化不明显。结论BMSCs和CMSCs移植治疗DMD,对肌肉组织有一定的修复作用,使DMD患者的运动功能得到改善,肌力有所提高,肌酸激酶较移植前下降。移植后复查肌电图波幅不同程度增高,运动单位增多,多相波减少。MSCs移植无不良反应,患者依从性好,是治疗DMD的新手段。Objective To observe the effect of combined transplantation of bone marrow mesenchymal stem cells （BMSCs） and umbilical cord blood mesenchymal stem cells （CMSCs） on progressive Duchemme muscular dystrophy （DMD）.Methods Two hundred sixty-nine DMD patients were given treatment of combined transplantation of autologous BMSCs and CMSCs.Patients were treated with recombinant human granulocute colony stimulating factors （rhG-CSF）,5～10 μg/kg,twice / d;with subcutaneous injection of myeloid stem cells,4 d;on days 5,with bone marrow collection,and bone marrow （100～180 ml） was collected from spina iliaca posterior superior under local anesthesia.After density gradient centrifugation,the bone marrow collected to isolate mononuclearcells 2.0×10^9,and Uitra culture solution was used to adjust cell count into 1×10^5/ml～1×10^6/ml,inoculated in 75 mm2 culture flasks,and the solution was changed after 24 h,total cells collected after days 7～10,the total number was 4.0×10^8/ml～1.5×10^9/ml.BMSCs were transplanted into proximal limb muscle of patients.Cord blood （80～160 ml） was collected,given by Ficoll density gradient centrifugatation,to isolate mononuclearcells and induced into CMSCs.CMSCs （1.0～4.8）×10^7 cell suspension were infused intravenously slowly,once/5～7 d,3 times.The muscle strength,time of 10-meter walk or wheelchair pushing,creatine kinase level,electromyogram （EMG） were observed 6 months after transplantation.Results In months 6 follow-up was preformed,muscle strength increased in 218 patients （81.0%）.The time of 10-meter walk or wheelchair pushing was shorten obviously,significant different from pre-transplantation （P〈0.05）.Two hundred thirty-five patients received myocardial enzyme review,188 of them （80%） had lower myocardial enzyme （P〈0.05）.Fifty-one had EMG review,32 of them （62.7%）had increased amplitude,motor unit increased,multi-phase wave reduced.Forty-seven patients had thigh muscle magnetic resonance imaging,without obvious chang

关 键 词：肌营养不良 骨髓间质干细胞 脐血间质干细胞 间质干细胞移植 

分 类 号：R746.2[医药卫生—神经病学与精神病学]