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

用来自多器官、人体芯片微生理系统的数据填充 MPS 数据库

• 批准号: 10435269
• 负责人: James J Hickman
• 金额: $ 7.8万
• 依托单位: HESPEROS, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-03 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10435269
• 关键词: Acute; Animal Testing; Antineoplastic Agents; Biochemical; Biological Assay; Cardiac; Cell Survival; Chronic; Clinical; Computer software; Custom; Data; Database Management Systems; Databases; Development; Devices; Disease; Disease model; Drug Combinations; Drug Compounding; Evaluation; Force of Gravity; Future; Generations; Goals; Human; Human body; In Vitro; Individual; Investigation; Journals; Legal patent; Liver; Malignant Neoplasms; Measurement; Measures; Mechanics; Metabolic; Methods; Modeling; Myocardial Ischemia; Myocardium; Neuromuscular Junction; Neurons; Non-Prescription Drugs; Organ; Output; Patient-Focused Outcomes; Patients; Peer Review; Pharmaceutical Preparations; Pharmacotherapy; Physiology; Procedures; Publications; Publishing; Resources; Serum; Skeletal Muscle; Structure; Surface; System; Technology; Therapeutic; Time; Tissues; Toxic effect; base; body on a chip; body system; cantilever; data format; data structure; database structure; drug discovery; flexibility; improved; innovation; interest; liver function; microphysiology system; non-invasive monitor; organ on a chip; parent grant; research clinical testing; shear stress; treatment response

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.

项目摘要/摘要： 正如《特别利益公告》中所述，有必要填充最近建立的 MPS数据库，包含芯片上器官系统生成的现有数据。拥有一个集中的、公共的 使用来自所有可用的MPS系统的数据的数据库将加快开发和接受 技术最终将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 药物发现中的测试。 在这份提案中，我们将汇编使用Hesperos的Human-on-a-ChipR收集和发布的数据 微生理系统(MPS)，包括作为父母拨款一部分收集的数据，并填充MPS 数据库。此外，我们将生成一个内部结构，以便于编译和提交 将未来数据添加到数据库中。作为Hesperos的多器官平台，这将是特别有价值的数据 是世界上最先进的基于人类的体外平台之一，具有几个独特的创新。第一, 该系统使用专利的无泵机械装置来循环使用可定制的、无血清的介质 重力，以获得双向流动(同时也有能力在需要时单向流动)。 其次，该系统具有高度的灵活性，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。这使得能够确定有效性和偏离目标的毒性 单一药物治疗和药物-药物联合治疗的效果，都在同一系统中。最后，平台 配备了生物机电设备，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(悬臂测量力)对心脏、骨骼肌、 神经组织和其他器官产生对器官功能实时变化的评估 对治疗的反应。因为我们的读数侧重于类似于临床评估的功能，而不是 使用我们的PKPD模型可以建立细胞活力的变化、实时临床相关性。这 这一能力能够评估治疗药物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 确定信息格式并将信息上传到MPS数据库。

项目成果

Piezoelectric BioMEMS Cantilever for Measurement of Muscle Contraction and for Actuation of Mechanosensitive Cells.

• DOI: 10.1557/mrc.2019.129
• 发表时间: 2019-12
• 期刊: MRS communications
• 影响因子: 1.9
• 作者: Coln EA;Colon A;Long CJ;Sriram NN;Esch M;Prot JM;Elbrecht DH;Wang Y;Jackson M;Shuler ML;Hickman JJ
• 通讯作者: Hickman JJ

Multiorgan Microphysiological Systems for Drug Development: Strategies, Advances, and Challenges.

• DOI: 10.1002/adhm.201701000
• 发表时间: 2018-01
• 期刊: Advanced healthcare materials
• 影响因子: 10
• 作者: Wang YI;Carmona C;Hickman JJ;Shuler ML
• 通讯作者: Shuler ML

Validation of an adipose-liver human-on-a-chip model of NAFLD for preclinical therapeutic efficacy evaluation.

• DOI: 10.1038/s41598-021-92264-2
• 发表时间: 2021-06-23
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Slaughter VL;Rumsey JW;Boone R;Malik D;Cai Y;Sriram NN;Long CJ;McAleer CW;Lambert S;Shuler ML;Hickman JJ
• 通讯作者: Hickman JJ

Stem cell derived phenotypic human neuromuscular junction model for dose response evaluation of therapeutics.

• DOI: 10.1016/j.biomaterials.2018.02.047
• 发表时间: 2018-06
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Santhanam N;Kumanchik L;Guo X;Sommerhage F;Cai Y;Jackson M;Martin C;Saad G;McAleer CW;Wang Y;Lavado A;Long CJ;Hickman JJ
• 通讯作者: Hickman JJ

Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system.

研究肝脏代谢对多器官人体芯片系统中脱靶心脏毒性的影响。

• DOI: 10.1016/j.biomaterials.2018.07.062
• 发表时间: 2018-11
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Oleaga C;Riu A;Rothemund S;Lavado A;McAleer CW;Long CJ;Persaud K;Narasimhan NS;Tran M;Roles J;Carmona-Moran CA;Sasserath T;Elbrecht DH;Kumanchik L;Bridges LR;Martin C;Schnepper MT;Ekman G;Jackson M;Wang YI;Note R;Langer J;Teissier S;Hickman JJ
• 通讯作者: Hickman JJ