Fig. 1.

Timeline of historical advancements and future advances in 3D cell culture systems. A summary of representative studies and breakthroughs leading to the establishment of various 3D culture systems has been presented. Reproduced with permission from Ref. [[28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60]]. Reorganization of dissociated sponge cells, amphibian pronephros, and multiple organs from an embryonic chick was first conducted. Reproduced with permission from Ref. [[28], [29], [30]]. The hanging drop method was established. Reproduced with permission from Ref. [29]. Perfect sphere-shaped aggregates were first established. Reproduced with permission from Ref. [32]. 3D organization of epithelium was conducted. Reproduced with permission from Ref. [33,34]. ESCs from mouse embryos were established. Reproduced with permission from Ref. [35]. Human ESCs were isolated and cultured. Reproduced with permission from Ref. [36]. Human and mouse iPSC were first established. Reproduced with permission from Ref. [37,38]. 3D intestinal organoids were formed by mouse intestinal stem cells. Reproduced with permission from Ref. [40]. Many researchers actively attempted to develop various organoids, such as intestine (2011), stomach (2010, 2014), liver (2013), inner ear (2013), pancreas (2013, 2015), lung (2014, 2015), kidney (2013), thyroid (2015), brain (2013), retina (2012), breast (2016), taste bud (2014), heart (2018), blood vessel (2019), and skin derived from ASCs and PSCs. Reproduced with permission from Ref. [[41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60]]. In the near future, applying microengineering- and nanoengineering-based platforms may facilitate increased production, improved reproducibility, and development of highly matured organoid systems.