A new technology for engineering axonal growth

描述（由申请人提供）：中枢神经系统（CNS）内的轴突再生仍然是神经科学中的一个基本挑战。最近，我们已经证明，如果轴突处于持续的机械张力下，大量（10/5）与中枢神经系统神经元培养结合的轴突将快速生长（8-10毫米/天），并且长得很远（约5厘米）。我们认为这一发现的影响可能是重大的。该技术提供了一种培养细胞移植物的方法，用于桥接白质中厘米长的病变，这种距离不易被如此大量的轴突通过，使用其他技术（例如，enshea鞘细胞移植，定向材料支架，控制释放）。此外，该模型为研究大量轴突加速生长的机制提供了一个机会，这在以前是不可能的。然而，该技术处于关键的初期阶段，存在风险——它没有被广泛使用或可供研究人员使用，而且我们不知道用该技术开发的轴突束是否具有可行的电生理功能。在这个提议中，我们将建立适当的技术基础设施，使用商业上可用的材料快速培养大量的细胞移植结构，为神经科学界创造一个更通用的资源。在这个系统的重新设计中嵌入的是允许测量结构的电生理特性。一旦发展起来，我们将利用这一技术提出一系列关于特定细胞骨架成分（神经丝）如何成为控制该技术生长速度的关键限制因素的研究。

DESCRIPTION (provided by applicant): Regenerating axons within the central nervous system (CNS) remains a fundamental challenge in neuroscience. Recently, we have shown that a large number (10/5) of axons integrated with CNS neuronal cultures will grow rapidly (8-10 mm/day) and over long distances ( >5 cm) if the axons are placed under a continuous mechanical tension. We feel the impact of this discovery could be significant. This technique provides a method to culture cell transplants for bridging lesions in the white matter that are centimeters long, distances that are not readily traversed with such a large number of axons using other techniques (e.g., ensheathing cell transplants, directed material scaffolds, controlled release). In addition, this model represents an opportunity to study the mechanisms of accelerated axonal growth in a large population of axons that was previously not possible. However, the technology is at a critical nascent stage with risk - it is not widely used or available to investigators, and we do not know if axonal tracts developed with this technique have viable electrophysiological function. In this proposed, we will build the appropriate technical infrastructure for rapidly culturing a large number of cell transplant constructs using commercially available materials, creating a more generalizable resource for the neuroscience community. Embedded within this re-design of the system is to allow for the measurement of electrophysiological properties of the constructs. Once developed, we use this to propose a series of studies on how a specific cytoskeletal component (neurofilaments) may be a key limiting factor in controlling the growth rate with this technique.