Populating MPS database with data from multi-organ, human-on-a-chip microphysiological systems

项目概要/摘要： 正如特别关注公告中所述，需要填充最近建立的 MPS数据库，包含由器官芯片系统生成的现有数据。有一个集中的，公共的 拥有所有可用MPS系统数据的数据库将加速开发和接受 这项技术最终能更快地为患者带来更好的治疗，同时显著减少对动物的需求。 药物发现的测试 在本提案中，我们将汇编使用Hesperos的芯片上的人类芯片收集和发布的数据， 微生理系统（MPS），包括作为母基金的一部分收集的数据，并填充MPS 数据库此外，我们将生成一个内部结构，以便于汇编和提交 未来的数据库。这将是特别有价值的数据，包括作为Hesperos的多器官平台 是世界上最先进的人体体外平台之一，具有几项独特的创新。第一、 该系统采用专利的无泵机制， 重力以获得双向流动（同时在需要时还具有单向流动的能力）。 其次，该系统具有高度灵活性，标准系统包含多达5个器官或屏障组织 这取决于感兴趣的应用。这使得能够确定疗效和脱靶毒性 单一药物治疗和药物-药物组合的效果，都在同一系统中。最后，平台 配备了生物机电设备，可以非侵入性地监测器官的功能变化， 化合物被引入、代谢和排泄。这些设备测量电气（MEA）和 机械（测量力的杠杆）对心脏，骨骼肌， 神经元组织和其他器官，产生器官的实时功能变化的评估， 对治疗的反应因为我们的读数关注的是类似于临床评估的功能，而不是 细胞活力的变化，可以使用我们的PKPD模型建立真实的时间临床相关性。这 这种能力能够评估治疗对人体的急性和慢性影响。 为此，Hesperos将首先建立必要的数据格式要求和转换程序， 为数据库生成最佳数据结构。然后，我们将现有的已发布数据转换为 确定格式并将信息上传到MPS数据库。

Project Summary/Abstract: As stated in the Notice of Special Interest announcement, there is a need to populate the recently established MPS database with existing data generated by organ-on-a-chip systems. Having a centralized, public database with data from all available MPS systems will accelerate development and acceptance of the technology ultimately bringing better therapies to patients faster while significantly reducing the need for animal testing in drug discovery. In this proposal, we will compile data collected and published using Hesperos’ Human-on-a-ChipⓇ microphysiological system (MPS), including data collected as part of the parent grant, and populate the MPS Database. Additionally, we will generate an internal structure that will facilitate compilation and submission of future data to the database. This will be especially valuable data to include as Hesperos’ multi-organ platform is among the worlds’ most advanced human-based in vitro platforms with several distinct innovations. First, the system uses a patented, pumpless mechanism to recirculate a customizable, serum-free medium using gravity to obtain bidirectional flow (while also having the capability for unidirectional flow when required). Second, the system is highly flexible with standard systems containing up to 5-organ or barrier tissues depending on the application of interest. This enables the ability to determine the efficacy and off-target toxic effects of both single drug treatments and drug-drug combinations, all in the same system. Lastly, the platform is equipped with bio-electromechanical devices that non-invasively monitor the functional changes to organs as compounds are introduced, metabolized, and excreted. These devices measure both the electrical (MEA’s) and mechanical (cantilevers to measure force) changes to organ-specific physiology for cardiac, skeletal muscle, neuronal tissues, and other organs producing an evaluation of the real-time functional changes of organs in response to treatment. Because our readouts focus on function that is analogous to clinical evaluations and not changes in cell viability, real time clinical correlations can be established using our PKPD models. This capability enables evaluation of both the acute and chronic effects of a therapeutic on the human body. For this effort, Hesperos will first establish data format requirements and conversion procedures necessary to produce the optimal data structure for the database. We will then convert existing, published data into the determined format and upload the information to the MPS Database.