A vascularized human organoid platform for disease modelling and preclinical testing

目前的临床前模型在很大程度上不能准确地描绘人类生理学。一方面，细胞单层生长的传统组织培养不能概括3D器官的复杂异质性。另一方面，啮齿动物等动物模型缺乏许多人类独有的特定生物学特征。因为我们用来研究人类疾病和预测药物反应的模型是不准确的，所以不可避免地，做出的预测也将同样不准确。这一观察结果反映在目前的药物发现管道中，因为许多使用单层培养和动物模型测试的药物由于人类患者体内不可预见的复杂性而在临床试验中失败。为了解决这一问题，我们正在寻求开发一种新一代人类疾病的临床前模型，准确地概括人类生理学。为了做到这一点，我们将来自人类干细胞的人造器官组织与活血管联系起来。然后，我们通过血管输送营养物质和药物化合物，方式与它们在人体内输送的方式相同。本系统中的人工器官在形态、功能、环境等方面直接模拟生理器官，为药物检测提供了有力的工具。为了建立我们的平台，我们聚集了一支多样化的学术研究团队，其中包括卫生研究和工程方面的专家以及几个私营部门合作伙伴。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，以实时监控药物反应。考虑到我们的团队和专业知识，我们独一无二地准备大幅提高临床前药物测试效率，不仅是在加拿大，而且是在全球药物发现管道，这是科学地改善人类健康的潜力。

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.