Blau H M, Webster C, Pavlath G K
Proc Natl Acad Sci U S A. 1983 Aug;80(15):4856-60. doi: 10.1073/pnas.80.15.4856.
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 gram 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 100-1,000 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 man 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. In contrast, the fibroblast yield and proliferative capacity from DMD samples did not differ from normal. Based on these findings, we propose a hypothesis for the etiology of DMD: 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.
在对杜氏肌营养不良症（DMD）患者培养的细胞进行克隆分析时，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。每克肌肉活检组织中肌母细胞的总产量降至正常水平的5%。在获得的DMD肌母细胞克隆中，很大一部分包含一类形态扁平且肿胀的细胞，这些细胞的代时延长，在细胞数量超过100 - 1000个后停止增殖，但可被诱导融合并形成肌管。在DMD患者的所有培养物中均检测到这种改变的肌肉表型，但在对照的肌母细胞中很少发现。到14岁时，这种细胞在DMD肌母细胞中所占比例高达90%。其余最初生长良好的DMD肌母细胞克隆，传代和进一步培养后增殖能力严重受损。最终，来自DMD肌肉组织的所有肌母细胞均表现出生长潜力缺陷。相比之下，DMD样本中的成纤维细胞产量和增殖能力与正常情况无异。基于这些发现，我们提出了一个关于DMD病因的假说：肌肉生长和维持需要分裂的肌母细胞，而DMD肌母细胞生长能力有限与该疾病特有的进行性肌肉退化直接相关。
