“人體芯片”系統(tǒng)是一些模型，能夠再現(xiàn)器官或一系列器官如何在身體內(nèi)起作用。想要獲得可以重現(xiàn)人體各項(xiàng)功能的人體芯片系統(tǒng)，就必須研制出這些神經(jīng)肌肉結(jié)點(diǎn)。大腦使用這些結(jié)點(diǎn)與身體內(nèi)的肌肉相互“交流”并控制身體的肌肉。
在研究中，美國布朗大學(xué)的赫爾曼·范登堡教授首先通過活體解剖方法從成人志愿者那兒收集了很多肌肉干細(xì)胞。中佛羅里達(dá)大學(xué)的納丁·郭進(jìn)行了一系列實(shí)驗(yàn)，利用不同濃度的細(xì)胞和不同的時(shí)間間隔以及其他參數(shù)，出了使肌肉細(xì)胞和脊髓細(xì)胞“快樂”結(jié)合的zui合適環(huán)境，zui終獲得了這些神經(jīng)肌肉結(jié)點(diǎn)。
該研究由美國國家衛(wèi)生研究院（NIH）下屬的國家神經(jīng)紊亂研究所資助，論文將發(fā)表在12月份的《生物材料》雜志上。該研究的、中佛羅里達(dá)大學(xué)的生物工程師詹姆斯·希克曼表示，他對(duì)這項(xiàng)研究的未來非常樂觀，傳統(tǒng)的動(dòng)物測試方法不僅緩慢、昂貴，而且常常失敗，阻礙了新藥研制和面世的進(jìn)程。
美國國家衛(wèi)生研究院、美國國防部研究計(jì)劃局以及美國食品和藥物管理局都在加速研制“人體芯片”模型，現(xiàn)在，投入該領(lǐng)域的資金至少有1.4億美元。這些研究團(tuán)隊(duì)的目的是出一些包含有各種各樣相互連接的小型器官的系統(tǒng)，采用實(shí)際中使用的方式來模擬人體功能。科學(xué)家們將可以借助這些系統(tǒng)，在藥物安全且合乎倫理地進(jìn)行人體臨床測試之前，先在人的細(xì)胞上測試其效果。這項(xiàng)技術(shù)有望比在老鼠和其它動(dòng)物身上進(jìn)行測試更加。
除了用來研制人體芯片模型，神經(jīng)肌肉結(jié)點(diǎn)本身也是非常重要的研究工具，它們在肌萎縮性側(cè)束硬化癥、脊髓受損以及其他退化性疾病等中也扮演著重要角色。科學(xué)家們表示，在更廣泛的基于芯片的模型被研制出來之前，技術(shù)能被用于測試治療這些疾病的新藥或其他療法。
Neuromuscular junction formation between human stem cell-derived motoneurons and human skeletal muscle in a defined system
Xiufang Guoa, Mercedes Gonzaleza, Maria Stancescua, b, Herman H. Vandenburghc, James J. Hickmana, d, ,
Functional in vitro models composed of human cells will constitute an important platform in the next generation of system biology and drug discovery. This study reports a novel human-based in vitro Neuromuscular Junction （NMJ） system developed in a defined serum-free medium and on a patternable non-biological surface. The motoneurons and skeletal muscles were derived from fetal spinal stem cells and skeletal muscle stem cells. The motoneurons and skeletal myotubes were compley differentiated in the co-culture based on morphological analysis and electrophysiology. NMJ formation was demonstrated by phase contrast microscopy, immunocytochemistry and the observation of motoneuron-induced muscle contractions utilizing time-lapse recordings and their subsequent quenching by d-Tubocurarine. Generally, functional human based systems would eliminate the issue of species variability during the drug development process and its derivation from stem cells bypasses the restrictions inherent with utilization of primary human tissue. This defined human-based NMJ system is one of the first steps in creating functional in vitro systems and will play an important role in understanding NMJ development, in developing high information content drug screens and as test beds in preclinical studies for spinal or muscular diseases/injuries such as muscular dystrophy, Amyotrophic lateral sclerosis and spinal cord repair.
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