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《特殊利益通知》公告中所述，需要填写最近设立的 MPS 数据库具有由片上器官系统生成的现有数据。 包含所有可用 MPS 系统数据的数据库将加速该系统的开发和接受 技术最终更快地为患者带来更好的治疗，同时显着减少对动物的需求 药物发现中的测试。 在此提案中，我们将汇编使用 Hesperos 的 Human-on-a-ChipⓇ 收集和发布的数据 微生理系统 (MPS)，包括作为家长资助的一部分收集的数据，并填充 MPS 此外，我们将生成一个内部结构，以方便编译和提交。 未来的数据将被纳入 Hesperos 的多器官平台，这将是特别有价值的数据。 是世界上最先进的人体体外平台之一，具有多项独特的创新。 该系统使用专利的无泵机制来再循环可定制的无血清培养基 重力以获得双向流动（同时在需要时也具有单向流动的能力）。 其次，该系统具有高度灵活性，标准系统最多可包含 5 个器官或屏障组织 这使得能够确定功效和脱靶毒性。 单一药物治疗和药物组合的效果都在同一个系统中。 配备生物机电设备，可以无创地监测器官的功能变化 这些设备可测量电学 (MEA) 和化合物的引入、代谢和排泄。 心脏、骨骼肌、器官特定生理学的机械（悬臂测量力）变化 神经组织和其他器官，对器官的实时功能变化进行评估 因为我们的读数重点是类似于临床评估的功能，而不是功能。 细胞活力的变化，可以使用我们的 PKPD 模型建立实时临床相关性。 能力能够评估治疗对人体的急性和慢性影响。 为此，Hesperos 将首先建立数据格式要求和必要的转换程序 然后，我们会将现有的已发布数据转换为数据库的最佳数据结构。 确定格式并将信息上传到 MPS 数据库。

项目成果

Self-contained, low-cost Body-on-a-Chip systems for drug development.

用于药物开发的独立、低成本片上系统。

• 发表时间: 2017-11
• 作者: Wang, Ying I;Oleaga, Carlota;Long, Christopher J;Esch, Mandy B;McAleer, Christopher W;Miller, Paula G;Hickman, James J;Shuler, Michael L
• 通讯作者: Shuler, Michael L

A functional hiPSC-cortical neuron differentiation and maturation model and its application to neurological disorders.

功能性 hiPSC-皮质神经元分化和成熟模型及其在神经系统疾病中的应用。

• 发表时间: 2022-01-11
• 影响因子: 5.9
• 作者: Autar, Kaveena;Guo, Xiufang;Rumsey, John W;Long, Christopher J;Akanda, Nesar;Jackson, Ma;Narasimhan, Narasimhan S;Caneus, Julbert;Morgan, Dave;Hickman, James J
• 通讯作者: Hickman, James J

Classical Complement Pathway Inhibition in a "Human-On-A-Chip" Model of Autoimmune Demyelinating Neuropathies.

自身免疫性脱髓鞘性神经病“人体芯片”模型中的经典补体途径抑制。

• 发表时间: 2022-06
• 影响因子: 4.6
• 作者: Rumsey, John W;Lorance, Case;Jackson, Ma;Sasserath, Trevor;McAleer, Christopher W;Long, Christopher J;Goswami, Arindom;Russo, Melissa A;Raja, Shruti M;Gable, Karissa L;Emmett, Doug;Hobson;Chopra, Manisha;Howard Jr, James F;Gupt
• 通讯作者: Gupt

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

用于药物开发的多器官微生理系统：策略、进展和挑战。

• 发表时间: 2018-01
• 影响因子: 10
• 作者: Wang, Ying I;Carmona, Carlos;Hickman, James J;Shuler, Michael L
• 通讯作者: Shuler, Michael L

A human in vitro platform for the evaluation of pharmacology strategies in cardiac ischemia.

用于评估心脏缺血药理学策略的人体体外平台。

• 发表时间: 2019-09
• 影响因子: 6
• 作者: Oleaga, Carlota;Jalilvand, Golareh;Legters, Gregg;Martin, Candace;Ekman, Gail;McAleer, Christopher W;Long, Christopher J;Hickman, James J
• 通讯作者: Hickman, James J