After the development of 3D cell culture methods in the middle of the last century and the plethora of data generated with this culture configuration up to date, it could be shown that a three-dimensional arrangement of cells in most of the cases leads to a more physiological behavior of the generated tissue. However, a major determinant for an organotypic function, namely, the dissolved oxygen concentration in the used in vitro-system, has been neglected in most of the studies. This is due to the fact that the oxygen measurement in the beginning was simply not feasible and, if so, disturbed the measurement and/or the in vitro-system itself. This is especially true for the meanwhile more widespread use of 3D culture systems. Therefore, the tissues analyzed by these techniques can be considered as the Schrödinger’s cat in 3D cell biology. In this perspective paper we will outline how the measurement and, moreover, the regulation of the dissolved oxygen concentration in vitro-3D culture systems could be established at all and how it may be possible to determine the oxygen concentration in organoid cultures and the respiratory capacity via mito stress tests, especially in spheroids in the size range of a few hundred micrometers, under physiological culture conditions, without disturbances or stress induction in the system and in a high-throughput fashion. By this, such systems will help to more efficiently translate tissue engineering approaches into new in vitro-platforms for fundamental and applied research as well as preclinical safety testing and clinical applications.

中文翻译：

---

体外生理氧测量——3D细胞生物学中的薛定谔猫

经过上世纪中叶 3D 细胞培养方法的发展以及迄今为止这种培养配置生成的大量数据，可以证明，在大多数情况下，细胞的三维排列会导致更多的结果。生成的组织的生理行为。然而，器官功能的一个主要决定因素，即所用容器中的溶解氧浓度体外系统，在大多数研究中都被忽视了。这是因为，一开始的氧气测量根本不可行，如果是这样，就会干扰测量和/或体外-系统本身。对于同时更广泛使用的 3D 培养系统来说尤其如此。因此，通过这些技术分析的组织可以被视为3D细胞生物学中的薛定谔猫。在这篇展望论文中，我们将概述如何测量以及调节溶解氧浓度体外-3D培养系统完全可以建立，以及如何通过线粒体压力测试确定类器官培养物中的氧气浓度和呼吸能力，特别是在生理培养条件下，尺寸范围为几百微米的球体，系统中没有干扰或应力诱导，并且以高通量方式。这样，此类系统将有助于更有效地将组织工程方法转化为新的方法体外-基础和应用研究以及临床前安全性测试和临床应用的平台。