摘要
目的:观察假肥大型肌营养不良症(PMD)患儿接受序贯式干细胞移植术(SCT)后抗肌萎缩蛋白(dystrophin)的表达、dystrophin基因和运动功能的变化。方法:采用自身对照法,2008年2月至2010年11月对5例8～14岁男性PMD患儿接受序贯式SCT[即依次进行脐带间充质干细胞(UCMSC)经静脉内移植-UCMSC肌肉内移植-单倍体相合造血干细胞移植术(Haplo-HSCT)]治疗,观察患儿血清酶学、基因分析、肌电图、肌肉活检及肌萎缩蛋白、造血重建的植入证据的变化。结果:移植后①血清肌酸激酶数值显著降低;②PCR-STR检测4例为完全供者型嵌合,1例3/6位点相合患儿未植入为完全受者型;③4例外显子缺失患儿外周血及骨髓表达正常基因型;④肌肉活检显示供受者嵌合状态,缺失的外显子弱阳性表达。肌细胞形态改善,肌萎缩蛋白间断弱阳性表达;⑤肌力及运动功能较治疗前无减退或改善。结论:PMD患儿接受序贯式SCT后缺失的外显子转变为正常基因型,肌细胞膜有肌萎缩蛋白阳性或弱阳性表达,可提高患儿的运动功能。
Aim：To investigate the feasibility and safety of therapy to 5 patients with pseudohypertrophic muscular dystrophy（PMD） who received stem cell transplantation in sequence by observing the change of motor function,muscle cytothesis and regeneration,expression of dystrophin and altering of depletion gene.Methods：After Medical Ethics Committee of PLA 463 Hospital gave license and patients＇ relatives signed informed consent,5 boys aged 8-14 with PMD were treated from February 2008 to November 2010.Firstly,intravenous umbilical cord mesenchymal stem cells（UCMSC） were transplanted.Secondly,intramuscular UCMSC were transplanted.Finally,haploidentical hematopoietic stem cells were transplanted（Haplo-HSCT）.The concentration of mononuclear cell（MNC） were（15.81-27.12）＊108/kg,CD34＋ cells（11.06-21.41）＊106/kg.Infusion of UCMSCs to prevent graft-versus-host disease（GVHD）：concentration of（2.5-4.9）＊106/kg were intravenous infused day-0,day-7 and day-14 after HSC transplantation.Sero-enzyme,implantation proof of donor HLA antigen,expression of depletion gene and dystrophin of myocyte membrane,motor function were detected after transplantation.Results：After Haplo-HSCT,complete donor engomphosis were found by polymerase chain reaction and short tandem repeat（PCR-STR） detecting patients＇ bone marrow and peripheral blood.Donor-recipient engomphosis were shown by muscle biopsy extracting DNA 85 days after transplantation,myocyte morphous were ameliorated and weakly positive dystrophin were expressed partly.Conclusion：Stem cell transplantation in sequence may benefit DMD patients.By transplantation depletion gene could be substitued,dystrophin of myocyte membrane expresses,sero-enzyme steps down significantly,motor function were improved.It could prevent the progression of disease and patient＇s condition is to be ameliorated continuously.
出处
《中国临床神经科学》
2011年第5期458-464,共7页
Chinese Journal of Clinical Neurosciences
基金
辽宁省重大课题攻关项目(编号:2008225009)
关键词
假肥大型肌营养不良症
序贯
脐带间充质干细胞
单倍体相合造血干细胞移植
抗肌萎缩蛋白
儿童
pseudohypertrophic muscular dystrophy
in sequence
umbilical cord mesenchymal stem cell
haploidentical hematopoietic stem cell transplantation
dystrophin
child
