I-Corps: In Vitro Cardiac Platform for Drug Discovery and Cardiotoxicity Screens

I-Corps：用于药物发现和心脏毒性筛选的体外心脏平台

• 批准号: 2335041
• 负责人: William Richardson
• 金额: $ 5万
• 依托单位: University of Arkansas
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2335041&HistoricalAwards=false
• 关键词: Corps; Vitro; Cardiac; Platform; Drug

The broader impact/commercial potential of this I-Corps project is the development of a drug discovery testing platform for potential heart treatments. Currently, most drug discovery testing begins with screening a new drug or therapeutic in traditional cell culture environments (e.g., petri dishes). However, this does not adequately represent the real biological context inside the human body. This is especially true for therapies targeting heart disease, where the cells are normally subjected to dynamic motion from the heart beating every second. The proposed technology aims to advance the next generation of heart disease medications using a cardiac tissue screening platform. The platform is designed to provide a physiologically relevant mechanical environment using electromagnetic controls and automated video tracking in order to expose tissues to the mechanical forces experienced within the body. Such a tool may hold potential for pharmaceutical companies, contract research organizations, and clinical cardiology practices/hospital systems. Ultimately, better discovery tools may lead to better therapies for improving human health and well-being.This I-Corps project is based on the development of heart tissue culture technology designed to mimic the mechanical environment of a beating heart for drug discovery applications. The proposed design of this platform uses computer-controlled electromagnets to subject 3-dimensional cardiac tissues to dynamic force-length relationships. The goal is to match the pressure and volume changes experienced by the heart in various heart disease conditions such as hypertension and aortic valve stenosis. In addition, the platform can produce disease-relevant metrics such as tissue stiffness, contractility, stroke work, and cardiac output curves, which directly translate to clinically relevant diagnostic metrics and outcome measures. The aim is to provide key merits that are not provided with existing approaches by subjecting tissues to full mechanical pressure. A physiologically correct mechanical environment may improve the success of therapy screens while physiologically relevant output metrics may help demonstrate clinical translatability. In addition, a dynamic mechanical environment may provide experimental versatility under desired testing conditions (e.g., normal vs. pressure-overload vs. volume-overload mechanics).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该I-Corps项目的更广泛的影响/商业潜力是开发用于潜在心脏治疗的药物发现测试平台。 当前，大多数药物发现测试始于在传统的细胞培养环境中筛查新药或治疗性（例如，培养皿）。 但是，这并不能充分代表人体内部的真实生物学环境。对于靶向心脏病的疗法尤其如此，在这种疗法中，通常每秒都会从心脏跳动的细胞进行动态运动。拟议的技术旨在使用心脏组织筛查平台推进下一代心脏病药物。 该平台旨在使用电磁控制和自动视频跟踪提供与生理相关的机械环境，以使组织暴露于身体内部经历的机械力。这样的工具可能对制药公司，合同研究组织和临床心脏病学实践/医院系统具有潜力。最终，更好的发现工具可能会带来更好的疗法，以改善人类健康和福祉。该I-Corps项目基于心脏组织培养技术的开发，旨在模仿殴打心脏的机械环境以进行药物发现应用。该平台的提议设计使用计算机控制的电磁体将三维心脏组织与动态力长度关系进行。 目的是匹配心脏在各种心脏病条件下（例如高血压和主动脉瓣狭窄）的压力和体积变化。 此外，该平台可以产生与疾病相关的指标，例如组织僵硬，收缩力，中风工作和心输出曲线，这些指标直接转化为临床相关的诊断指标和结果指标。 目的是通过使组织承受完全的机械压力来提供现有方法未提供的关键优点。 生理上正确的机械环境可以改善治疗筛查的成功，而生理相关的产出指标可能有助于证明临床转换性。 此外，动态的机械环境可以在所需的测试条件下提供实验性的多功能性（例如，正常与压力超负荷与数量超过负载机制）。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的审查标准来通过评估来获得支持的。