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质囊泡在细胞间 沟通，最终目标是阐明新的沟通机制 参与疾病病理学。为了实现这一目标，我们正在开发新的生物分析工具 包括组织培养和灌注系统 组织切片和基于分离的生物测定，用于直接和选择性定量 微流体体积中的外来体。在未来5年，我们的计划目标是：1）实现 我们的组织培养灌注系统的关键系统改进将实现高灵敏度 分泌因子的测量; 2）开发基于分离的新模式 特异性地定制以定量外泌体释放的免疫测定;以及3）应用这些免疫测定， 技术来研究通过细胞外的昼夜节律协调的假设 脑视交叉上核的囊泡释放。我们设想我们的研究 在生物分析和细胞外囊泡研究中实现新的研究维度 社区，最终导致新的疗法，靶向失调的细胞间 在神经和代谢紊乱方面的交流。

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.