New technologies for in situ measurement of exosome release from brain slice cultures

摘要 我们的研究计划旨在了解细胞外脂小泡在细胞间的作用 通信，最终目标是阐明新的通信机制 与疾病病理有关的。为了实现这一目标，我们正在开发新的生物分析工具 包括用于从体外释放的外切体取样的组织培养和灌流系统 直接和选择性定量的组织切片和基于分离的生物测定 微流体体积中的外体。未来5年，我们的计划目标是：1)实现 我们的组织培养灌流系统的关键系统改进将实现高灵敏度 分泌因子的测定；2)开发一种基于分离的新模式 专为外切体释放量身定做的免疫测定法；以及3)应用这些 通过细胞外研究昼夜节律协调假说的技术 大脑视交叉上核内的囊泡释放。我们设想我们的研究将 在生物分析和细胞外囊泡研究中实现新的研究维度 社区，最终导致针对调节失调的细胞间的新疗法 神经和代谢紊乱中的沟通。

Abstract Our research program aims to understand the role of extracellular lipid vesicles in intercellular communication, with the ultimate goal of elucidating new mechanisms of communication involved in disease pathologies. To achieve this, we are developing new bioanalysis tools including tissue culture and perfusion systems for sampling exosomes released from ex vivo tissue slices, and separations-based bioassays for the direct and selective quantitation of exosomes in microfluidic volumes. For the next 5 years, our program goals are: 1) to achieve key system refinements of our tissue culture perfusion system that will enable high sensitivity measurements of secreted factors; 2) to develop a novel mode of separations-based immunoassay tailored specifically to the quantitation of exosome release; and 3) to apply these technologies to investigate a hypothesis of circadian rhythm coordination via extracellular vesicle release in the suprachiasmatic nucleus of the brain. We envision that our research will enable new dimensions of study in the bioanalytical and extracellular vesicle research communities, ultimately leading to new therapies that target dysregulated intercellular communications in neurological and metabolic disorders.