IFlowPlate - a universal platform for vascularizing organoids

为了提高临床前阶段药物发现的精确度，对先进的基于人类的组织模型的需求日益增长，这些模型补充了动物和基于细胞的分析的使用。近年来，有机化合物已成为一种很有前途的替代品。来自干细胞的有机类化合物可以概括器官的发育过程，并模拟器官的生物学复杂性。然而，大多数器官模型缺乏可灌流的血管网络，而血管网络是控制广泛器官功能的最普遍的生物结构。为了解决这个问题，我们开发了一种平台技术(IFlowPlatform)，它可以生长一系列可灌流的血管网络，按需使有机化合物血管化。利用该平台，我们证明了结肠类器官和肝脏球体可以被血管化，以模拟复杂的生物过程，如血管内药物和免疫细胞递送以及炎症反应。从我们最初的市场评估中，我们对这项技术产生了极大的兴趣，并与主要制药公司和生命科学试剂分销商形成了多次合作。然而，我们仍然可以解决一些与工程设计相关的问题，以更好地使我们的技术与最终用户的需求保持一致。在这项拟议的研究中，我们寻求(目标1)在IFlowBoard中建立单向血管流动，(AIM 2)访问用于屏障功能分析的有机物的管腔，以及(AIM 3)将IFlowBoard从当前的384孔板格式转换为学术用户使用的96或24孔板格式。这项工作将解决终端用户的关键问题，显著扩大应用范围，并为行业采用平台技术做好更好的准备。该团队在开发创新的组织培养平台和将其商业化方面有着良好的记录，并计划通过一家生物技术初创公司将IFlowPlatform商业化。我们已经开始与多家制药公司和CRO合作测试我们的技术，并吸引了一家风险投资公司的早期投资。

To improve the precision of drug discovery at the preclinical stage, there is a growing demand for advanced human-based tissue models that complement the use of animals and cell-based assays. In recent years, organoids have emerged as a promising alternative. Organoids derived from stem cells can recapitulate the developmental process and model the biological complexity of an organ. However, most organoid models lack perfusable blood vessel networks which are the most prevalent biological structures that control a wide range of organ functions. To solve this problem, we developed a platform technology (IFlowPlate) that can grow an array of perfusable blood vessel networks to vascularize organoids on demand. Using the platform, we demonstrated that colon organoids and liver spheroids can be vascularized to model complex biological processes, such as intravascular drug and immune cell delivery and inflammatory response. From our initial market assessment, we received overwhelming interest in the technology and have formed multiple collaborations with major pharmaceutical companies and life science reagent distributors. However, there are still a number of engineering design-related questions that we can address to better align our technology with the needs of the end-users. In this proposed research, we seek (AIM 1) to establish uni-directional vascular flow in IFlowPlate, (AIM 2) to access the lumen of organoids for barrier function assays, and (AIM 3) to convert the IFlowPlate from the current 384-well plate format to a 96- or 24- well plate format for academic users. This work will resolve the key concerns from the end-users, significantly expand the application, and better prepare the platform technology for industry adoption. The team has a track record of developing and commercializing innovative tissue culture platforms and plans to commercialize IFlowPlate through a biotech startup company. We have initiated collaboration with multiple pharmaceutic companies and CROs to test our technology and attracted early investments from a venture capital firm.