近日，Development在線發(fā)表了美國密蘇里大學(xué)科學(xué)家的研究成果,。當(dāng)肌肉受傷時(shí)，會(huì)發(fā)出信號(hào)呼喚一種叫做“衛(wèi)星細(xì)胞”（satellite cells）的休眠成熟干細(xì)胞“醒來”,，投身到修復(fù)工作中,。新的研究發(fā)現(xiàn)發(fā)現(xiàn)，即使衛(wèi)星細(xì)胞遠(yuǎn)離受傷肌肉,，也有向?qū)檫@些干細(xì)胞引路,，讓它們?cè)诩∪饨M織內(nèi)旅行，趕來幫助修復(fù)受傷部位,。這一發(fā)現(xiàn)有助于為肌肉失調(diào)類疾病如肌營養(yǎng)不良癥找到更有效的新療法,。
在實(shí)驗(yàn)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(zhì)制成,，然后用延時(shí)顯微鏡追蹤觀察衛(wèi)星細(xì)胞在“條紋”上移動(dòng)的情況。他們發(fā)現(xiàn),，一種名為蝶素（ephrin）的蛋白質(zhì)的幾個(gè)亞型對(duì)衛(wèi)星細(xì)胞有同樣的功效,，即細(xì)胞一接觸到蝶素制造的條紋，就會(huì)立刻轉(zhuǎn)彎,，改變行進(jìn)方向,。密蘇里大學(xué)文理學(xué)院生物科學(xué)副教授、邦德生命科學(xué)中心研究員科內(nèi)利森解釋說：“干細(xì)胞的運(yùn)動(dòng)就像讓一個(gè)人蒙住眼睛在過道上走,，他們會(huì)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(xì)胞沿著更直線的方向到達(dá)發(fā)來求救信號(hào)的遠(yuǎn)處。”
實(shí)驗(yàn)還發(fā)現(xiàn)，用蝶素條紋給衛(wèi)星細(xì)胞以不同的信號(hào),，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(shí)現(xiàn)過,。研究人員認(rèn)為,，蝶素可能調(diào)控著幾個(gè)不同的步驟：從衛(wèi)星細(xì)胞離開干細(xì)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(xì)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(xì)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(fù)基因
>>延伸閱讀：Nature：心臟損傷修復(fù)機(jī)制
>>延伸閱讀：美國科學(xué)家將脂肪干細(xì)胞轉(zhuǎn)化為肌肉細(xì)胞
>>延伸閱讀：美國研究人讓骨髓干細(xì)胞長成老鼠心臟肌肉
>>延伸閱讀：成人干細(xì)胞可以修復(fù)受損的肌肉
>>延伸閱讀：Cell：科學(xué)家發(fā)現(xiàn)能修復(fù)受損肌肉的干細(xì)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.
