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成人干细胞修复损伤肌肉

当肌肉受伤时,称为卫星细胞的休眠成人干细胞被发出醒来的信号,投身于修复肌肉工作中。密苏里大学的研究人员最近发现远端的卫星细胞如何能帮助修复,他们正在研究干细胞如何在组织中旅游。这种知识最后能帮助医生更有效地治疗类似于肌肉萎缩症样的肌肉疾病,在这种疾病中,肌肉易受伤,病人的卫星细胞丧失修复能力。

当你的肌肉受伤时,他们向卫生细胞发出来修复他们的求救信号,那些卫星细胞知道到什么地方制造更多的肌细胞最终成为新肌肉组织。Cornelison博士这样说,他是艺术和科学学院的生物学助理教授,也是结合生命科学中心的研究人员。"目前还没有治疗人类肌肉萎缩症有效的基于卫星细胞的治疗方法。当前治疗方法的问题是每平方厘米需要注射100个干细胞,病人的单块肌肉则多达4000次注射,因为干细胞不能分散很远。如果我们能知道正常健康的卫星细胞如何能在肌肉人里四处旅行,临床研究人员就可能利用此信息改变注射细胞如何作用,改善治疗的效果。"

在一项新研究里,Cornelison'实验室的研究人员用时间显微照像仪跟踪卫生细胞在涂在载玻片上的不同蛋白狭窄肌纤维上的运动。研究人员发现名为肝配蛋白的几种版本对卫星细胞有相同作用:接触过肝配蛋白组成的条纹肌的细胞立刻向回转,向新的方向旅行。

Cornelison说:"干细胞运动与人蒙着眼睛是过道的方法相似,他们将感觉墙壁。因为长的平行肌纤维表面有肝配蛋白,肝配蛋白可能正好帮助卫生细胞朝着远方求救信号沿直线运动。"

如果研究人员给卫星细胞发出在培养基中分化形成肌纤维的信号,课题组也发现他们能用肝配蛋白的条纹使自己平行排列,方式就是肌纤维在生物体中的排列,但是在培养皿中无法这样做。这引起研究人员思考,肝配蛋白事实上可能调节几个不同的步骤,这些步骤是从大量遍布肌肉的干细胞获取所必需的,也是组织、仿造新肌纤维所必需的。

Cornelison说:"我们确实很兴奋,相对于肌肉萎缩症患者自己的细胞,或是治疗上注射的细胞而言,这些发现很有潜力解释许多关于卫星细胞在健康肌肉行为方式的迷惑。如果我们确实幸运,我们可能发现能让这些病人生活有所不同的东西,也是我们最想要的。"

论文发表在期刊《发育》(Development)11版上,作者包括来自密苏里大学生物科学部的学生DannyStark,RowanKarvas和AshleySiegel。研究由国家卫生研究所(NIH)资助。

Eph/ephrin interactions modulate muscle satellite cell motility and patterning

Dannv 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.