Development of magnetic force biotechnology to facilitate neural regeneration

开发磁力生物技术促进神经再生

• 批准号: EP/X014126/1
• 负责人: Neil Telling
• 金额: $ 102.69万
• 依托单位: Keele University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX014126%2F1
• 关键词: Development; magnetic; force; biotechnology; facilitate

The central nervous system (CNS) consists of both the brain and spinal cord and is responsible for co-ordinating activity across our entire body. Such co-ordination requires the precise connections of billions of neurons (nerve cells), sometimes across distances of up to 0.5 metres long. These connections are made using long, thin fibres known as axons, which project from the cell body and allow the transport of electrical impulses between the neurons (somewhat like the electrical circuits that connect components in a computer).Damage to the neural circuitry in the CNS can be caused by acute trauma (for example spinal cord injury) or following the development of neurological disorders such as Parkinson's disease. Within the CNS, it is the spinal cord that contains the neuronal circuits that govern complex movements such as walking. Unfortunately, the ability of axons in the CNS to naturally regenerate is extremely limited, and so the functional deficits that result from damage to the brain or spinal cord, can persist indefinitely. Millions of people worldwide are currently living with the disabling effects of such damage, and so new approaches to find potential treatments that could restore these neural connections are desperately needed.This project builds on a previously successful collaboration to use physical sciences and bioengineering approaches to manipulate neurons using remote magnetic forces. Here we will investigate whether magnetic force methods could be used to remotely guide axon re-growth to reconnect neural circuits and restore function. To do this we will design and develop new controllable magnetic force devices. We will use these systems to target specialist microscopic magnetic nanoparticles loaded into intracellular compartments in the axons known as endosomes. In addition, we will explore the use of advanced genetic modification techniques to prepare neuronal cells that can biosynthesize magnetic nanoparticles internally. To test these methodologies, we will investigate the effects of magnetic forces on a novel biological model of spinal cord injury, that incorporates living sections of tissue cultured from the rat cortex and spinal cord.The project will bring together a wide-reaching, cross-disciplinary team with expertise in physics and materials science, neuroscience, electrophysiology, synthetic biology, and neurosurgery. If successful, the project will provide the crucial foundation technology required to translate the methods towards pre-clinical and ultimately clinical treatments of spinal cord injury. It will also have significant impact on research in other areas of neuroscience and neurological disorders which seek to re-establish circuits in the CNS, such as Parkinson's disease.

中枢神经系统（CNS）由大脑和脊髓组成，负责协调我们整个身体的活动。这种协调需要数十亿个神经元（神经细胞）的精确连接，有时距离长达0.5米。这些连接是由称为轴突的长而细的纤维形成的，轴突从细胞体伸出，允许神经元之间的电脉冲传输（有点像连接计算机中组件的电路）。中枢神经系统中神经回路的损伤可能由急性创伤（例如脊髓损伤）或神经系统疾病（如帕金森病）的发展引起。在中枢神经系统中，脊髓包含控制复杂运动（如行走）的神经元回路。不幸的是，中枢神经系统中轴突自然再生的能力极其有限，因此由脑或脊髓损伤引起的功能缺陷可能无限期地持续下去。目前全世界有数百万人生活在这种损伤的致残影响中，因此迫切需要找到新的方法来寻找可能恢复这些神经连接的潜在治疗方法。该项目建立在以前成功的合作基础上，利用物理科学和生物工程方法，使用远程磁力操纵神经元。在这里，我们将研究磁力方法是否可以用于远程引导轴突再生，以重新连接神经回路和恢复功能。为此，我们将设计和开发新的可控磁力装置。我们将使用这些系统来靶向加载到轴突中称为内体的细胞内隔室中的专业微观磁性纳米颗粒。此外，我们将探索使用先进的基因修饰技术来制备可以在内部生物合成磁性纳米颗粒的神经元细胞。为了测试这些方法，我们将研究磁力对脊髓损伤的新型生物模型的影响，该模型包括从大鼠皮层和脊髓培养的活体组织切片。该项目将汇集一个广泛的跨学科团队，他们具有物理学和材料科学，神经科学，电生理学，合成生物学和神经外科学的专业知识。如果成功，该项目将提供将这些方法转化为脊髓损伤临床前和最终临床治疗所需的关键基础技术。它也将对神经科学和神经系统疾病的其他领域的研究产生重大影响，这些领域寻求在中枢神经系统中重建电路，如帕金森病。