Department of Bioengineering, University of California, San Diego, CA, USA.
Dev Med Child Neurol. 2013 Mar;55(3):264-70. doi: 10.1111/dmcn.12027. Epub 2012 Dec 5.
Satellite cells are the stem cells residing in muscle responsible for skeletal muscle growth and repair. Skeletal muscle in cerebral palsy (CP) has impaired longitudinal growth that results in muscle contractures. We hypothesized that the satellite cell population would be reduced in contractured muscle.
We compared the satellite cell populations in hamstring muscles from participants with CP contracture (n=8; six males, two females; age range 6-15y; Gross Motor Function Classification System [GMFCS] levels II-V; 4 with hemiplegia, 4 with diplegia) and from typically developing participants (n=8; six males, two females, age range 15-18y). Muscle biopsies were extracted from the gracilis and semitendinosus muscles and mononuclear cells were isolated. Cell surface markers were stained with fluorescently conjugated antibodies to label satellite cells (neural cell adhesion molecule) and inflammatory and endothelial cells (CD34 and CD4 respectively). Cells were analyzed using flow cytometry to determine cell populations.
After gating for intact cells a mean of 12.8% (SD 2.8%) were determined to be satellite cells in typically developing children, but only 5.3% (SD 2.3%; p<0.05) in children with CP. Hematopoietic and endothelial cell types were equivalent in typically developing children and children with CP (p>0.05) suggesting the isolation procedure was valid.
A reduced satellite cell population may account for the decreased longitudinal growth of muscles in CP that develop into fixed contractures or the decreased ability to strengthen muscle in CP. This suggests a unique musculoskeletal disease mechanism and provides a potential therapeutic target for debilitating muscle contractures.
卫星细胞是存在于肌肉中的干细胞,负责骨骼肌肉的生长和修复。脑瘫(CP)患者的骨骼肌纵向生长受损,导致肌肉挛缩。我们假设挛缩肌肉中的卫星细胞群体减少。
我们比较了 CP 挛缩患者(n=8;6 名男性,2 名女性;年龄范围 6-15 岁;粗大运动功能分类系统 [GMFCS] 水平 II-V;4 名偏瘫,4 名四肢瘫)和发育正常的参与者(n=8;6 名男性,2 名女性,年龄范围 15-18 岁)的腘绳肌卫星细胞群。从 gracilis 和 semitendinosus 肌肉中提取肌肉活检,并分离单核细胞。用荧光标记的抗体对细胞表面标志物进行染色,以标记卫星细胞(神经细胞黏附分子)和炎症细胞和内皮细胞(分别为 CD34 和 CD4)。使用流式细胞术分析细胞群体。
在门控完整细胞后,发育正常儿童的卫星细胞平均为 12.8%(SD 2.8%),而 CP 儿童仅为 5.3%(SD 2.3%;p<0.05)。在发育正常的儿童和 CP 儿童中,造血细胞和内皮细胞类型是等同的(p>0.05),这表明分离过程是有效的。
卫星细胞群体减少可能是 CP 肌肉纵向生长减少导致固定挛缩的原因,也可能是 CP 肌肉无力增强的原因。这表明存在独特的肌肉骨骼疾病机制,并为致残性肌肉挛缩提供了潜在的治疗靶点。