微制造动态脑类器官共培养,以评估表面几何形状对组合体形成的影响。
Microfabricated dynamic brain organoid cocultures to assess the effects of surface geometry on assembloid formation.
发表日期:2024 Aug
作者:
Camille Cassel de Camps, Sabra Rostami, Vanessa Xu, Chen Li, Paula Lépine, Thomas M Durcan, Christopher Moraes
来源:
Biotechnology Journal
摘要:
类器官已成为研究发育和疾病的宝贵工具。组合体是通过整合多种类器官类型来创建更复杂的模型而形成的。然而,类器官整合形成组合体的过程仍不清楚,并且可能在最终的类器官结构中发挥重要作用。在这里,开发了一个微流体平台,允许单独培养不同的类器官类型,并提供部分控制所得类器官表面几何形状的能力。然后,去除微制造的屏障使得成形和定位的类器官相互作用并形成组合体。当中脑和无引导的大脑类器官被允许以限定的间距组装时,当两种类型的类器官融合在一起时,观察并定量测量中脑类器官的轴突投射和无引导的类器官中的细胞迁移。轴突投影方向在统计上偏向于其他中脑类器官,并且发现不受引导的类器官表面几何形状会影响细胞侵袭。该平台提供了一种工具来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、轴突靶向和组合体形成机制方面具有价值。© 2024 作者。生物技术杂志由 Wiley‐VCH GmbH 出版。
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.© 2024 The Author(s). Biotechnology Journal published by Wiley‐VCH GmbH.