A new technology for engineering axonal growth

描述(由申请人提供)：在中枢神经系统(CNS)内再生轴突仍然是神经科学中的一个基本挑战。最近，我们发现大量(10/5)与中枢神经系统神经元培养整合的轴突将迅速生长(8-10 mm/天)和长距离(5厘米)，如果轴突被放置在持续的机械张力下。我们认为这一发现的影响可能是巨大的。这项技术提供了一种培养细胞移植的方法，用于桥接白质中长达几厘米的病变，使用其他技术(例如，包膜细胞移植、定向材料支架、控制释放)，这些距离不容易被如此大量的轴突跨越。此外，这个模型提供了一个研究大量轴突加速生长的机制的机会，这在以前是不可能的。然而，这项技术正处于一个具有风险的关键新生阶段-它没有被广泛使用或研究人员可用，我们也不知道用这项技术开发的轴索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来快速培养大量的细胞移植构建物，为神经科学界创造一个更具普遍性的资源。在该系统的重新设计中嵌入的是允许测量构造的电生理属性。一旦开发出来，我们就用它来提出一系列研究，研究特定的细胞骨架成分(神经丝)如何成为使用这项技术控制生长速度的关键限制因素。

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.