DEFECTIVE MYOBLASTS IDENTIFIED IN DUCHENNE MUSCULAR-DYSTROPHY
DEFECTIVE MYOBLASTS IDENTIFIED IN DUCHENNE MUSCULAR-DYSTROPHY
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DOI：
10.1073/pnas.80.15.4856
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发表时间：
1983-01-01
期刊：
影响因子：
--
通讯作者：
PAVLATH, GK
中科院分区：
文献类型：
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作者：
BLAU, HM;WEBSTER, C;PAVLATH, GK
从杜氏肌营养不良症（DMD）患者培养的细胞克隆分析中发现，卫星细胞（成熟肌纤维的单核前体细胞）的增殖能力存在缺陷。每克肌肉活检的成肌细胞的总产量下降到正常的5%。在获得的DMD成肌细胞克隆中，大部分包含具有增加的世代时间并且停止增殖超过100-1000个细胞但可被诱导融合并形成肌管的扁平扩张细胞的形态学类别。在DMD患者的所有培养物中检测到改变的肌肉表型，但在对照组的成肌细胞中很少发现。到14岁时，它包含多达90%的DMD成肌细胞。剩余的DMD成肌细胞克隆最初生长良好，但在传代和进一步培养时增殖能力严重受损。最终，所有来自DMD肌肉组织的成肌细胞都表现出有缺陷的生长潜力。DMD样本的成纤维细胞产量和增殖能力与正常无差异。提出了DMD的病因学假说。分裂成肌细胞是肌肉生长和维持所必需的，DMD成肌细胞生长的有限能力与该疾病的进行性肌肉变性特征直接相关。
A defect in the proliferative capacity of satellite cells, mononucleated precursors of mature muscle fibers, was found in clonal analyses of cells cultured from Duchenne muscular dystrophy (DMD) patients. The total yield of myoblasts per g of muscle biopsy was decreased to 5% of normal. Of the DMD myoblast clones obtained, a large proportion contained a morphological class of flat distended cells that had an increased generation time and ceased to proliferate beyond 100-1000 cells but could be induced to fuse and form myotubes. The altered muscle phenotype was detected in all cultures from DMD patients but was rarely found among myoblasts of controls. By age 14 yr, it comprised as many as 90% of DMD myoblasts. The remaining DMD myoblast clones, which initially grew well, had severely impaired proliferative capacity upon passage and further cultivation. Eventually all myoblasts from DMD muscle tissue exhibited defective growth potential. The fibroblast yield and proliferative capacity from DMD samples did not differ from normal. A hypothesis for the etiology of DMD was proposed. Dividing myoblasts are required for muscle growth and maintenance, and the limited capacity of DMD myoblasts to grow is directly related to the progressive muscle degeneration characteristic of the disease.