A vascularized human organoid platform for disease modelling and preclinical testing

用于疾病建模和临床前测试的血管化人体类器官平台

• 批准号: 549533-2020
• 负责人: Attisano, LilianaL
• 金额: $ 31.69万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Collaborative Health Research Projects
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744111
• 关键词: vascularized; human; organoid; platform; disease

Current preclinical models in a large part fail to accurately portray human physiology . On onehand, traditional tissue culture in which cells are grown in monolayer do not recapitulate thecomplex heterogeneity of 3D organs. On the other hand, animal models such as rodents lackmany specific biological features that are unique to humans. Because the models we areusing to study human disease and predict drug responses are inaccurate, it is inevitable thatthe predictions made will be similarly inaccurate. This observation is reflected in the currentdrug discovery pipeline, as many drugs that are tested using monolayer culture and animalmodels fail in clinical trials due to unforeseen complexities in human patients. To address thisissue, we are seeking to develop a next generation preclinical model of human disease thataccurately recapitulates human physiology. To do this, we link up artificial organ tissuesderived from human stem cells to living blood vessels. We then deliver through the bloodvessels nutrients and drug compounds in the same manner that they are delivered in thehuman body. The artificial organs in our system directly mimic physiological organs in termsof morphology, function, and environment thus serving as a powerful tool for drug testing. Toestablish our platform, we have gathered a diverse team of academic researchers includingexperts in health research and engineering and several private sector partners. Together, wewill harness our platform to develop sophisticated models of the brain and gut as well asadvanced imaging frameworks to monitor drug responses in real time. Considering our teamand expertise, we are thus uniquely poised to drastically improve preclinical drug testingefficiency not only in Canada but also for global drug discovery pipelines which as thepotential to scientifically improve human health.

目前的临床前模型在很大程度上不能准确地描绘人体生理学。一方面，细胞在单层中生长的传统组织培养不能再现三维器官的复杂异质性。另一方面，啮齿类动物等动物模型缺乏许多人类特有的特定生物学特征。由于我们用于研究人类疾病和预测药物反应的模型是不准确的，因此不可避免地，所做的预测也将同样不准确。这一观察结果反映在当前的药物发现管道中，因为许多使用单层培养和动物模型进行测试的药物由于在人类患者中不可预见的复杂性而在临床试验中失败。为了解决这个问题，我们正在寻求开发下一代人类疾病的临床前模型，以准确地概括人类生理学。为此，我们将从人类干细胞中提取的人造器官组织与活血管连接起来。然后我们通过血管输送营养物质和药物化合物，就像它们在人体内输送一样。人体系统中的人造器官在形态、功能和环境上直接模仿生理器官，从而成为药物检测的有力工具。为了建立我们的平台，我们聚集了一个多元化的学术研究团队，包括健康研究和工程专家以及一些私营部门的合作伙伴。我们将共同利用我们的平台开发复杂的大脑和肠道模型，以及先进的成像框架，以实时监测药物反应。考虑到我们的团队和专业知识，我们不仅可以大幅提高加拿大的临床前药物测试效率，还可以提高全球药物发现管道的效率，这是科学改善人类健康的潜力。