當(dāng)肌肉受傷時,,稱為衛(wèi)星細(xì)胞的休眠成人干細(xì)胞被發(fā)出醒來的信號,投身于修復(fù)肌肉工作中,。密蘇里大學(xué)的研究人員最近發(fā)現(xiàn)遠(yuǎn)端的衛(wèi)星細(xì)胞如何能幫助修復(fù),,他們正在研究干細(xì)胞如何在組織中旅游。這種知識最后能幫助醫(yī)生更有效地治療類似于肌肉萎縮癥樣的肌肉疾病,,在這種疾病中,,肌肉易受傷,,病人的衛(wèi)星細(xì)胞喪失修復(fù)能力,。
當(dāng)你的肌肉受傷時,他們向衛(wèi)生細(xì)胞發(fā)出來修復(fù)他們的求救信號,,那些衛(wèi)星細(xì)胞知道到什么地方制造更多的肌細(xì)胞最終成為新肌肉組織,。Cornelison博士這樣說,他是藝術(shù)和科學(xué)學(xué)院的生物學(xué)助理教授,,也是結(jié)合生命科學(xué)中心的研究人員,。"目前還沒有治療人類肌肉萎縮癥有效的基于衛(wèi)星細(xì)胞的治療方法。當(dāng)前治療方法的問題是每平方厘米需要注射100個干細(xì)胞,,病人的單塊肌肉則多達(dá)4000次注射,,因為干細(xì)胞不能分散很遠(yuǎn)。如果我們能知道正常健康的衛(wèi)星細(xì)胞如何能在肌肉人里四處旅行,,臨床研究人員就可能利用此信息改變注射細(xì)胞如何作用,,改善治療的效果,。"
在一項新研究里,Cornelison'實驗室的研究人員用時間顯微照像儀跟蹤衛(wèi)生細(xì)胞在涂在載玻片上的不同蛋白狹窄肌纖維上的運動,。研究人員發(fā)現(xiàn)名為肝配蛋白的幾種版本對衛(wèi)星細(xì)胞有相同作用:接觸過肝配蛋白組成的條紋肌的細(xì)胞立刻向回轉(zhuǎn),,向新的方向旅行。
Cornelison說:"干細(xì)胞運動與人蒙著眼睛是過道的方法相似,,他們將感覺墻壁,。因為長的平行肌纖維表面有肝配蛋白,肝配蛋白可能正好幫助衛(wèi)生細(xì)胞朝著遠(yuǎn)方求救信號沿直線運動,。"
如果研究人員給衛(wèi)星細(xì)胞發(fā)出在培養(yǎng)基中分化形成肌纖維的信號,,課題組也發(fā)現(xiàn)他們能用肝配蛋白的條紋使自己平行排列,方式就是肌纖維在生物體中的排列,,但是在培養(yǎng)皿中無法這樣做,。這引起研究人員思考,肝配蛋白事實上可能調(diào)節(jié)幾個不同的步驟,,這些步驟是從大量遍布肌肉的干細(xì)胞獲取所必需的,,也是組織、仿造新肌纖維所必需的,。
Cornelison說:"我們確實很興奮,,相對于肌肉萎縮癥患者自己的細(xì)胞,或是治療上注射的細(xì)胞而言,,這些發(fā)現(xiàn)很有潛力解釋許多關(guān)于衛(wèi)星細(xì)胞在健康肌肉行為方式的迷惑,。如果我們確實幸運,我們可能發(fā)現(xiàn)能讓這些病人生活有所不同的東西,,也是我們最想要的,。"
論文發(fā)表在期刊《發(fā)育》(Development)11版上,作者包括來自密蘇里大學(xué)生物科學(xué)部的學(xué)生DannyStark,,RowanKarvas和AshleySiegel,。研究由國家衛(wèi)生研究所(NIH)資助。(生物谷bioon.com)
doi:10.1242/dev.068411
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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.