## 1 Introduction  
Cell culture, an important technique in basic and preclinical research, is a cost-effective way of reducing the number of experimental animals during the drug discovery process [1]. Although two-dimensional (2D) cell culture is a universal and valuable method, it has its limitations [2]; for example, the cells proliferate and grow in a single layer and thus lack the cell-cell and extracellular matrix (ECM) interactions present in native tissues and cells. In addition, the cells are stretched and undergo a cytoskeletal rearrangement, acquiring artificial polarity and expressing abnormal genes and proteins [3]. Unlike tissues in an in vivo environment, 2D systems cannot provide a complex and dynamic microenvironment for cells, leading to potentially invalid findings [4; 5]. For these reasons, the majority of compounds discovered in 2D cell culture during drug discovery fail in clinical trials [6]. Therefore, it is important to establish an in vitro cell culture system that can more realistically simulate the dynamics of cells in vivo. Three-dimensional (3D) culture systems are an excellent in vitro model that can mimic in vivo processes, such as embryogenesis, morphogenesis, and organogenesis [7]. Spheroids and organoids are cellular aggregates with complex cell-cell adhesion that generate gradients of nutrients, gases, growth factors, and signaling factors. These structures can replicate the cellular microenvironment observed in real tissues and simulate in vivo cell dynamics more realistically. Human induced pluripotent stem cells (iPSCs), the discovery of which has helped stem cell research make great strides, can be used to generate spheroids and organoids, which were employed in the elucidation of pathological conditions [8; 9; 10; 11; 12]and drug discovery [8; 13; 14; 15]. Recently, organoids derived from iPSCs generated from patients with intractable diseases were used to elucidate the disease mechanisms [16; 17]. In the field of drug discovery, the validation of drug efficacy using organoids derived from human iPSCs in the early stage of in vitro testing is expected to reduce the possibility of candidate compound failure before initiating clinical trials. Indeed, drug testing using iPSC-derived organoids has shown comparable results to those of drugs already used for treatment [18]. Because the use of spheroids and organoids is expected to increase in the future, developing methods for their efficient production is important. Various 3D culture methods have been tried and implemented. Conventional 3D culture methods can be broadly classified into four types: micropatterned forced flotation, hanging drop, swirling culture or spinner flask, and force-driven methods [19]. The micropatterned forced flotation method involves well plates in which cells deposited inside the microwells adhere to each other in three dimensions [20; 21; 22], as well as low-adhesion plates in which areas with different cell adhesion properties are patterned to prevent cell aggregation [23]. Microfluidic systems are a type of micropatterned forced flotation that combines both the target cells and matrix components to create spheroids on microfluidic chips with microgel beads [24; 25]. The hanging drop method utilizes the surface tension of the culture medium to form droplets, while the interface with the air is used as a microwell [26; 27; 28]. The spinner flask or swirling culture (bioreactor) is a method of spheroidization via collision and contact between cells through continuous swirling and agitation of the culture medium in which cells are dispersed [29; 30]; this method also includes microfluidic types on a smaller scale [31; 32; 33]. Force-driven methods include magnetic methods where nanoparticles, such as iron oxide, gold, and poly-L-lysine, are attached to the cell surface. Spheroids are formed via the following: magnetic forces [34]; electric methods in which an external force, such as an electric field, is applied [35]; and acoustic tweezers [36].