I-Corps: Integrated Multi-Tissue Human Models for Drug Development

这个I-Corps项目更广泛的影响/商业潜力是能够在临床试验阶段之前预测人类对治疗方案的反应。通过在人体模型中测试药物毒性和疗效，药物可以更快地进入市场，风险更小，成本更低，同时可能减少动物试验的使用。目前，平均需要10年时间和28亿美元才能将药物推向市场，其中大部分成本是由于后期药物失败。在人体器官系统中筛选可预测体内条件的药物的能力将更好地为药物开发各个阶段的"去/不去"决策提供信息。更广泛的影响包括能够创建“盘中”临床试验，其中可以在临床试验之前确定从药物中获益最多的患者人群与风险人群。使用患者特异性细胞可以开发动物模型无法重现疾病的疾病模型，以及罕见疾病的药物测试，其中受影响的个体数量有限，无法进行标准临床试验。这个I-Corps项目利用了一个模块化平台，旨在通过血管连接在生理上整合多个人体组织工程器官模型，模拟器官在人体中如何相互连接。连接的组织工程模型在整合之前单独成熟，以提供准确再现健康和疾病的器官水平反应所需的高度生物保真度。人类诱导多能干细胞的使用使患者特异性细胞和基因编辑细胞的使用成为可能，并为进一步推进精准医学计划提供了平台。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is the ability to predict how humans will respond to therapeutic treatment options before the clinical trial stage. By testing drug toxicity and efficacy in a human model, drugs can get to market more quickly, with less risk and lower costs, while potentially reducing the use of animal testing. Currently it takes an average of 10 years and $2.8B to get a drug to market, with the majority of the cost due to late-stage drug failures. The ability to screen drugs in human organ systems that are predictive of in vivo conditions will better inform "go/no-go" decision-making throughout the stages of drug development. Broader impacts include the ability to create clinical trials "in-a-dish" where patient populations that will benefit the most from the drug versus those that would be at risk can be determined before clinical testing. Use of patient-specific cells may enable the development of disease models where animal models failed to recapitulate the disease, as well as drug testing for rare diseases, where the limited number of affected individuals prevents the standard clinical trial format. This I-Corps project utilizes a modular platform designed to physiologically integrate multiple human tissue engineered organ models though vascular connections that mimic how organs are connected to one another in the human body. The connected tissue engineered models are individually matured prior to integration to provide the high biological fidelity needed to accurately recapitulate organ level responses of health and disease. The use of human induced pluripotent stem cells enables the use of patient-specific cells and gene-edited cells, as well as provides a platform to further precision medicine initiatives.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.