近日，Development在線發(fā)表了美國密蘇里大學科學家的研究成果,。當肌肉受傷時,，會發(fā)出信號呼喚一種叫做“衛(wèi)星細胞”（satellite cells）的休眠成熟干細胞“醒來”，投身到修復工作中,。新的研究發(fā)現(xiàn)發(fā)現(xiàn),，即使衛(wèi)星細胞遠離受傷肌肉，也有向導為這些干細胞引路,，讓它們在肌肉組織內(nèi)旅行,，趕來幫助修復受傷部位。這一發(fā)現(xiàn)有助于為肌肉失調類疾病如肌營養(yǎng)不良癥找到更有效的新療法,。
在實驗中,，研究人員在玻璃片上涂上狹窄的“條紋”，這些條紋由不同的蛋白質制成,，然后用延時顯微鏡追蹤觀察衛(wèi)星細胞在“條紋”上移動的情況,。他們發(fā)現(xiàn)，一種名為蝶素（ephrin）的蛋白質的幾個亞型對衛(wèi)星細胞有同樣的功效,，即細胞一接觸到蝶素制造的條紋,，就會立刻轉彎，改變行進方向,。密蘇里大學文理學院生物科學副教授,、邦德生命科學中心研究員科內(nèi)利森解釋說：“干細胞的運動就像讓一個人蒙住眼睛在過道上走，他們會通過觸摸墻壁來感知路徑,。而長長的,、平行的肌纖維表面有這些蝶素蛋白，從而能幫助衛(wèi)星細胞沿著更直線的方向到達發(fā)來求救信號的遠處,。”
實驗還發(fā)現(xiàn),，用蝶素條紋給衛(wèi)星細胞以不同的信號，能讓它們平行排列形成肌纖維,，這正是活組織中的肌纖維形式,，此前在培養(yǎng)皿中從未實現(xiàn)過。研究人員認為,，蝶素可能調控著幾個不同的步驟：從衛(wèi)星細胞離開干細胞群,，分布到所有的肌肉，到最后形成有組織且紋理清晰的新纖維,，這些步驟必不可少,。
人類肌營養(yǎng)不良癥患者的肌肉很容易受傷，按現(xiàn)有療法,，每平方厘米需要100次干細胞注射,，病人一塊肌肉約要注射4000次,?？苾?nèi)利森說,，如果我們掌握了正常衛(wèi)星細胞是怎樣在組織內(nèi)部旅行的，臨床上就能利用這一信息,，改變注射方式,，找到更高效的療法。(生物谷Bioon.com)
>>延伸閱讀：Nat. Genet.：研究發(fā)現(xiàn)新的肌肉修復基因
>>延伸閱讀：Nature：心臟損傷修復機制
>>延伸閱讀：美國科學家將脂肪干細胞轉化為肌肉細胞
>>延伸閱讀：美國研究人讓骨髓干細胞長成老鼠心臟肌肉
>>延伸閱讀：成人干細胞可以修復受損的肌肉
>>延伸閱讀：Cell：科學家發(fā)現(xiàn)能修復受損肌肉的干細胞
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.
