一种集成功能性血管化类器官芯片的微流控平台。
A microfluidic platform integrating functional vascularized organoids-on-chip.
机构信息
Univ. Grenoble Alpes, CEA, IRIG/BGE, BIOMICS, 38000, Grenoble, France.
Univ. Grenoble Alpes, CEA, LETI, DTBS, 38000, Grenoble, France.
出版信息
Nat Commun. 2024 Feb 16;15(1):1452. doi: 10.1038/s41467-024-45710-4.
The development of vascular networks in microfluidic chips is crucial for the long-term culture of three-dimensional cell aggregates such as spheroids, organoids, tumoroids, or tissue explants. Despite rapid advancement in microvascular network systems and organoid technologies, vascularizing organoids-on-chips remains a challenge in tissue engineering. Most existing microfluidic devices poorly reflect the complexity of in vivo flows and require complex technical set-ups. Considering these constraints, we develop a platform to establish and monitor the formation of endothelial networks around mesenchymal and pancreatic islet spheroids, as well as blood vessel organoids generated from pluripotent stem cells, cultured for up to 30 days on-chip. We show that these networks establish functional connections with the endothelium-rich spheroids and vascular organoids, as they successfully provide intravascular perfusion to these structures. We find that organoid growth, maturation, and function are enhanced when cultured on-chip using our vascularization method. This microphysiological system represents a viable organ-on-chip model to vascularize diverse biological 3D tissues and sets the stage to establish organoid perfusions using advanced microfluidics.
在微流控芯片中发展血管网络对于长期培养三维细胞聚集体(如球体、类器官、肿瘤球体或组织外植体)至关重要。尽管微血管网络系统和类器官技术取得了快速进展,但在组织工程中使类器官血管化仍然是一个挑战。大多数现有的微流控设备都不能很好地反映体内流动的复杂性,并且需要复杂的技术设置。考虑到这些限制,我们开发了一个平台,用于建立和监测围绕间充质和胰岛球体的内皮网络的形成,以及从多能干细胞生成的血管类器官的形成,这些球体和类器官在芯片上培养长达 30 天。我们表明,这些网络与富含内皮细胞的球体和血管类器官建立了功能连接,因为它们成功地为这些结构提供了血管内灌注。我们发现,当使用我们的血管化方法在芯片上培养时,类器官的生长、成熟和功能得到增强。这个微生理系统代表了一种可行的血管化多种生物 3D 组织的器官芯片模型,并为使用先进的微流控技术进行类器官灌注奠定了基础。