CAREER: Engineering nervous tissue in vitro: Discovering the mechanisms of rapid axon stretch growth.

职业：体外工程神经组织：发现轴突快速拉伸生长的机制。

• 批准号: 0747615
• 负责人: Bryan Pfister
• 金额: $ 42.43万
• 依托单位: New Jersey Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-15 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0747615&HistoricalAwards=false
• 关键词: CAREER; Engineering; nervous; tissue; vitro

Pfister0747615The research objective of this proposal is to define and analyze how stretching forces, associated with the growth of an organism, initiate unique neurobiological mechanisms to accommodate stretch growth of axons, driving the natural and rapid formation of long nerves and white matter tracts. In a developing embryo, axons navigate via a growth cone over seeming large distances to reach their targets. However, well after axons integrate with their targets and establish synaptic connections, animals and their nervous systems continue to grow several orders of magnitude. It is conceivable that stretching forces, exerted on axons by the enlarging body, serves as the mechanism that initiates and maintains stretch growth of the axon cylinder. An in vitro tissue engineering method has been developed to recapitulate this fundamentally different and rapid form of axonal growth that occurs during an organism's development. Far exceeding the rate of growth cone extension, this new-found form of nervous system growth, extreme axon stretch growth, can reach at least 10mm per day. These investigations mapped out the biomechanical boundaries that allow integrated axon bundles to quickly adapt to escalating stretch-growth rates, producing large axon fascicles 10cm in length and potentially much longer. Remarkably, these extreme stretch growth conditions also stimulate expansion of axon caliber, while maintaining a normal cytoskeletal ultrastructure and the ability to convey action potentials. Surprisingly, few studies have examined the effects of mechanical stretch on the rapid growth potential of axons. Axon stretch growth presents a novel opportunity to greatly expand upon the current understanding of nervous system growth with real potential to discover new targets to accelerate regeneration, offering an unexplored direction in nerve repair. Additional scientific benefits of this model could be the ability to engineer structured nervous tissue to study the pathology of nervous system diseases or the neurophysiological behavior of an organized network of neurons. Students at all levels will be included in this exciting and challenging opportunity to explore new territory in bioengineering and neuroscience. Opportunities and mentoring will also be provided for students with disabilities as well as encouragement and assistance for high school students with disabilities and their college plans.

PFISTER0747615该提案的研究目标是定义和分析与生物体生长相关的拉伸力如何启动独特的神经生物学机制，以适应轴突的伸展生长，推动长长神经和白物质的自然和快速形成。在发育中的胚胎中，轴突在看起来很大的距离上穿过生长锥以达到目标。但是，在轴突与目标集成并建立突触连接后，动物及其神经系统继续增加了几个数量级。可以想象的是，伸展力通过扩大的身体施加在轴突上，是启动和维持轴突圆柱体伸展生长的机制。已经开发了一种体外组织工程方法，以概括这种在生物体发育过程中发生的根本不同和快速形式的轴突生长。这种新发现的神经系统生长，极端轴突拉伸生长的新发现形式远远超过了生长锥扩展的速度，每天至少达到10mm。这些研究绘制了生物力学边界，这些边界使整合的轴突束快速适应了伸展增长速率的升级，从而产生了长度10厘米的大轴突束，并且可能更长。值得注意的是，这些极端拉伸的生长条件还刺激了轴突口径的扩张，同时保持正常的细胞骨架超微结构和传达动作电位的能力。令人惊讶的是，很少有研究检查机械拉伸对轴突快速生长潜力的影响。 Axon伸展增长提供了一个新的机会，可以极大地扩展对神经系统生长的当前理解，其真正的潜力是发现新目标以加速再生，从而在神经修复方面提供了未开发的方向。该模型的其他科学益处可能是能够设计结构化的神经组织来研究神经元网络的神经系统疾病的病理或神经生理行为。各个级别的学生将包括在探索生物工程和神经科学领域的新领域的激动人心和挑战的机会中。还将为残疾学生提供机会和指导，并为残疾高中生及其大学计划提供鼓励和帮助。