近日，Development在线发表了美国密苏里大学科学家的研究成果。当肌肉受伤时，会发出信号呼唤一种叫做“卫星细胞”（satellite cells）的休眠成熟干细胞“醒来”，投身到修复工作中。新的研究发现发现，即使卫星细胞远离受伤肌肉，也有向导为这些干细胞引路，让它们在肌肉组织内旅行，赶来帮助修复受伤部位。这一发现有助于为肌肉失调类疾病如肌营养不良症找到更有效的新疗法。
在实验中，研究人员在玻璃片上涂上狭窄的“条纹”，这些条纹由不同的蛋白质制成，然后用延时显微镜追踪观察卫星细胞在“条纹”上移动的情况。他们发现，一种名为蝶素（ephrin）的蛋白质的几个亚型对卫星细胞有同样的功效，即细胞一接触到蝶素制造的条纹，就会立刻转弯，改变行进方向。密苏里大学文理学院生物科学副教授、邦德生命科学中心研究员科内利森解释说：“干细胞的运动就像让一个人蒙住眼睛在过道上走，他们会通过触摸墙壁来感知路径。而长长的、平行的肌纤维表面有这些蝶素蛋白，从而能帮助卫星细胞沿着更直线的方向到达发来求救信号的远处。”
实验还发现，用蝶素条纹给卫星细胞以不同的信号，能让它们平行排列形成肌纤维，这正是活组织中的肌纤维形式，此前在培养皿中从未实现过。研究人员认为，蝶素可能调控着几个不同的步骤：从卫星细胞离开干细胞群，分布到所有的肌肉，到最后形成有组织且纹理清晰的新纤维，这些步骤必不可少。
人类肌营养不良症患者的肌肉很容易受伤，按现有疗法，每平方厘米需要100次干细胞注射，病人一块肌肉约要注射4000次。科内利森说，如果我们掌握了正常卫星细胞是怎样在组织内部旅行的，临床上就能利用这一信息，改变注射方式，找到更高效的疗法。(生物谷Bioon.com)
>>延伸阅读：Nat. Genet.：研究发现新的肌肉修复基因
>>延伸阅读：Nature：心脏损伤修复机制
>>延伸阅读：美国科学家将脂肪干细胞转化为肌肉细胞
>>延伸阅读：美国研究人让骨髓干细胞长成老鼠心脏肌肉
>>延伸阅读：成人干细胞可以修复受损的肌肉
>>延伸阅读：Cell：科学家发现能修复受损肌肉的干细胞
doi:10.1242/dev.068411
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Eph/ephrin interactions modulate muscle satellite cell motility and patterning
Danny A. Stark, Rowan M. Karvas, Ashley L. Siegel and D. D. W. Cornelison
During development and regeneration, directed migration of cells, including neural crest cells, endothelial cells, axonal growth cones and many types of adult stem cells, to specific areas distant from their origin is necessary for their function. We have recently shown that adult skeletal muscle stem cells (satellite cells), once activated by isolation or injury, are a highly motile population with the potential to respond to multiple guidance cues, based on their expression of classical guidance receptors. We show here that, in vivo, differentiated and regenerating myofibers dynamically express a subset of ephrin guidance ligands, as well as Eph receptors. This expression has previously only been examined in the context of muscle-nerve interactions; however, we propose that it might also play a role in satellite cell-mediated muscle repair. Therefore, we investigated whether Eph-ephrin signaling would produce changes in satellite cell directional motility. Using a classical ephrin ‘stripe’ assay, we found that satellite cells respond to a subset of ephrins with repulsive behavior in vitro; patterning of differentiating myotubes is also parallel to ephrin stripes. This behavior can be replicated in a heterologous in vivo system, the hindbrain of the developing quail, in which neural crest cells are directed in streams to the branchial arches and to the forelimb of the developing quail, where presumptive limb myoblasts emigrate from the somite. We hypothesize that guidance signaling might impact multiple steps in muscle regeneration, including escape from the niche, directed migration to sites of injury, cell-cell interactions among satellite cell progeny, and differentiation and patterning of regenerated muscle.
