Cell-Fiber-Based 3D Tissue Array for Drug Response Assay

Abstract: 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 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.