Department of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo, Tokyo, 202-8585, Japan.
Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8505, Japan.
Sci Rep. 2022 May 12;12(1):7870. doi: 10.1038/s41598-022-11670-2.
For the establishment of a reproducible and sensitive assay system for three-dimensional (3D) tissue-based drug screening, it is essential to develop 3D tissue arrays with uniform shapes and high cell numbers that prevent cell death in the center of the tissue. In recent years, 3D tissue arrays based on spheroids have attracted increased attention. However, they have only been used in specific tissues with hypoxic regions, such as cancer tissues, because nutrient deprivation and hypoxic regions are formed in the core as spheroids grow. Herein, we propose a method to array cell-encapsulated tube-like tissue (cell fiber (CF)) with diameters < 150 μm to prevent nutrient deprivation and hypoxia using a device that can fix the CFs, section them in uniform sizes, and transfer them to a 96-well plate. We fabricated the arrays of CF fragments from cell lines (GT1-7), cancer cells (HeLa), mouse neural stem cells (mNSCs) and differentiated mNSCs, and performed drug response assays. The array of CF fragments assessed the drug response differences among different cell types and drug responses specific to 3D tissues. The array of CF fragments may be used as a versatile drug screening system to detect drug sensitivities in various types of tissues.
为了建立可重现且敏感的基于三维（3D）组织的药物筛选测定系统，开发具有均匀形状和高细胞数的 3D 组织阵列以防止组织中心的细胞死亡至关重要。近年来，基于球体的 3D 组织阵列引起了越来越多的关注。然而，它们仅在具有缺氧区域的特定组织中使用，例如癌症组织，因为随着球体的生长，核心会形成营养剥夺和缺氧区域。在此，我们提出了一种使用可以固定 CF 的设备来排列直径<150μm 的细胞包封管状组织（细胞纤维（CF））的方法，以防止使用该设备时的营养剥夺和缺氧，该设备可以将 CF 切成均匀的大小，并将其转移到 96 孔板中。我们从细胞系（GT1-7）、癌细胞（HeLa）、小鼠神经干细胞（mNSC）和分化的 mNSC 中制造了 CF 片段的阵列，并进行了药物反应测定。CF 片段的阵列评估了不同细胞类型之间的药物反应差异以及 3D 组织特有的药物反应。CF 片段的阵列可用作通用的药物筛选系统，以检测各种类型组织中的药物敏感性。
