A new technology for engineering axonal growth

工程轴突生长的新技术

• 批准号: 6877974
• 负责人: DAVID F MEANEY
• 金额: $ 18.33万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6877974
• 关键词: action potentials; axon; cell transplantation; electrophysiology; electrostimulus; fluorescence microscopy; laboratory mouse; mechanical stress; messenger RNA; neurofilament; neurofilament proteins; neurogenesis; technology /technique development; tissue /cell culture

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.

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基本挑战。最近，我们已经证明，如果将轴突置于连续的机械条件下，大量（10/5）与 CNS 神经元培养物整合的轴突将快速生长（8-10 毫米/天）并长距离（> 5 厘米）紧张。我们认为这一发现的影响可能是巨大的。该技术提供了一种培养细胞移植物的方法，用于桥接白质中的病变，这些病变的长度为厘​​米，而使用其他技术（例如，鞘细胞移植、定向材料支架、控释）很难用如此大量的轴突穿越这些距离。 ）。此外，该模型还提供了一个研究大量轴突加速轴突生长机制的机会，这在以前是不可能的。然而，该技术仍处于关键的初级阶段，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。在本提案中，我们将建立适当的技术基础设施，使用市售材料快速培养大量细胞移植结构，为神经科学界创造更通用的资源。嵌入在系统的重新设计中的是允许测量结构的电生理特性。一旦开发完成，我们将利用它提出一系列研究，探讨特定的细胞骨架成分（神经丝）如何成为使用该技术控制生长速率的关键限制因素。