IFlowPlate - a universal platform for vascularizing organoids

IFlowPlate - 血管化类器官的通用平台

• 批准号: 566853-2021
• 负责人: Zhang, Boyang
• 金额: $ 9.11万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Idea to Innovation
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=728732
• 关键词: IFlowPlate; universal; platform; vascularizing; organoids

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.

为了提高临床前阶段药物发现的精确度，人们越来越需要先进的基于人类的组织模型，以补充动物和基于细胞的测定。近年来，类器官已成为一种有前途的替代方案。来源于干细胞的类器官可以概括发育过程并模拟器官的生物复杂性。然而，大多数类器官模型缺乏可灌注的血管网络，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（IFlowPlate），可以生长一系列可灌注的血管网络，以根据需要使类器官血管化。使用该平台，我们证明了结肠类器官和肝脏球状体可以血管化以模拟复杂的生物过程，例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来看，我们对该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建立了多个合作伙伴关系。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（AIM 1）在IFlowPlate中建立单向血管流，（AIM 2）进入类器官的管腔进行屏障功能测定，以及（AIM 3）将IFlowPlate从当前的384孔板格式转换为96或24孔板格式供学术用户使用。这项工作将解决最终用户的关键问题，显著扩展应用程序，并为行业采用更好地准备平台技术。该团队在开发和商业化创新组织培养平台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IFlowPlate商业化。我们已经开始与多家制药公司和CRO合作，以测试我们的技术，并吸引了风险投资公司的早期投资。