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

点击翻译按钮获取中文摘要

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.