Department of Biomedical Engineering, McGill University, Montréal, QC, Canada.
Department of Chemical Engineering, McGill University, Montréal, QC, Canada.
Biotechnol J. 2024 Aug;19(8):e2400070. doi: 10.1002/biot.202400070.
Organoids have emerged as valuable tools for the study of development and disease. Assembloids are formed by integrating multiple organoid types to create more complex models. However, the process by which organoids integrate to form assembloids remains unclear and may play an important role in the resulting organoid structure. Here, a microfluidic platform is developed that allows separate culture of distinct organoid types and provides the capacity to partially control the geometry of the resulting organoid surfaces. Removal of a microfabricated barrier then allows the shaped and positioned organoids to interact and form an assembloid. When midbrain and unguided brain organoids were allowed to assemble with a defined spacing between them, axonal projections from midbrain organoids and cell migration out of unguided organoids were observed and quantitatively measured as the two types of organoids fused together. Axonal projection directions were statistically biased toward other midbrain organoids, and unguided organoid surface geometry was found to affect cell invasion. This platform provides a tool to observe cellular interactions between organoid surfaces that are spaced apart in a controlled manner, and may ultimately have value in exploring neuronal migration, axon targeting, and assembloid formation mechanisms.
类器官已成为研究发育和疾病的重要工具。组装类器官是通过整合多种类器官类型来创建更复杂的模型。然而，类器官整合形成组装类器官的过程尚不清楚，并且可能在最终的类器官结构中发挥重要作用。在这里，开发了一种微流控平台，该平台允许对不同类型的类器官进行单独培养，并提供部分控制所得类器官表面几何形状的能力。然后去除微加工的屏障，允许成形和定位的类器官相互作用并形成组装类器官。当中脑和无指导的脑类器官被允许在它们之间具有确定的间隔进行组装时，从中脑类器官的轴突投射和无指导的类器官中的细胞迁移被观察到，并随着两种类型的类器官融合在一起而被定量测量。轴突投射方向在统计上偏向于其他中脑类器官，并且无指导的类器官表面几何形状被发现影响细胞入侵。该平台提供了一种工具，可以观察以受控方式间隔开的类器官表面之间的细胞相互作用，并且最终可能在探索神经元迁移、轴突靶向和组装体形成机制方面具有价值。
