A high-throughput spheroid fusion platform for the templated-assembly of 3D neuromuscular junctions

用于 3D 神经肌肉接头模板组装的高通量球体融合平台

基本信息

批准号：
NC/X002187/1
负责人：
Fabrice GIELEN
金额：
$ 25.07万
依托单位：
UNIVERSITY OF EXETER
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=NC%2FX002187%2F1
关键词：
throughput spheroid fusion platform templated

项目摘要

Neurons help control movement by sending conveying electrical impulses from the brain and spinal cord to the muscles. The connection between the neurons and muscles happens in the human body at specific places called neuromuscular junctions (NMJ). Understanding the interactions between neurons and muscle cells is crucial to understand neuromuscular development and dysfunction. At the moment, there are no available human three-dimensional models that can be used to study this junction, hence animal models are routinely used instead. However, animal NMJ differs significantly from the human ones. Hence, it is critical to develop accurate human models of the NMJ. In the past few years, our team has developed novel technologies that permit the formation of lab-grown tissue that can be used to recapitulate human physiology.In this project, we will create a novel in-vitro model neuromuscular junction to alleviate the need for animal models. We will grow both neurons and muscle cells into three dimensional cultures and force them to assemble using networks of microtraps. We will generate for the first time truly 3D organoids with hundreds of such junctions per experiment, a number at least one order of magnitude higher than previous attempts. The junctions will be validated by measuring muscle contraction upon chemical stimulation of the neurons. This will ensure that the models we create have the highest relevance to human physiology and can be used as a platform for future biomedical research.

神经元通过从大脑和脊髓向肌肉发送电脉冲来帮助控制运动。神经元和肌肉之间的连接发生在人体内称为神经肌肉接头 (NMJ) 的特定位置。了解神经元和肌肉细胞之间的相互作用对于了解神经肌肉发育和功能障碍至关重要。目前，还没有可用的人体三维模型可用于研究这种连接，因此通常使用动物模型。然而，动物 NMJ 与人类 NMJ 存在显着差异。因此，开发准确的 NMJ 人体模型至关重要。在过去的几年中，我们的团队开发了新技术，可以形成实验室生长的组织，可用于重现人类生理学。在这个项目中，我们将创建一种新型的体外神经肌肉接头模型，以减轻对神经肌肉接头的需求。动物模型。我们将把神经元和肌肉细胞培养成三维培养物，并使用微陷阱网络迫使它们组装。我们将首次生成真正的 3D 类器官，每个实验有数百个这样的连接，数量比之前的尝试至少高一个数量级。将通过测量神经元化学刺激后的肌肉收缩来验证连接点。这将确保我们创建的模型与人类生理学具有最高的相关性，并且可以用作未来生物医学研究的平台。