Microfluidic three-dimensional cell culture of stem cells for high-throughput analysis

Abstract

Although the recent advances in stem cell engineering have gained a great deal of attention due to their high potential in clinical research, the applicability of stem cells for preclinical screening in the drug discovery process is still challenging due to difficulties in controlling the stem cell microenvironment and the limited availability of high-throughput systems. Recently, researchers have been actively developing and evaluating three-dimensional (3D) cell culture-based platforms using microfluidic technologies, such as organ-on-a-chip and organoid-on-a-chip platforms, and they have achieved promising breakthroughs in stem cell engineering. In this review, we start with a comprehensive discussion on the importance of microfluidic 3D cell culture techniques in stem cell research and their technical strategies in the field of drug discovery. In a subsequent section, we discuss microfluidic 3D cell culture techniques for high-throughput analysis for use in stem cell research. In addition, some potential and practical applications of organ-on-a-chip or organoid-on-a-chip platforms using stem cells as drug screening and disease models are highlighted.

Keywords: High-throughput screening; Microfluidic technology; Stem cell; Three-dimensional cell culture.

Figure 1

Representative examples of high-throughput screening microfluidic systems using stem cells based on organ-on-a-chip or organoid-on-a-chip. A: An engineered perfusable liver platform using induced pluripotent stem cell (iPSC). The iPSC-derived hepatocytes were aggregated as three-dimensional (3D) organoids and encapsulated in Poly (ethylene glycol) diacrylate hydrogel. These cells were loaded in a C-trap chip subjected to perfusion for a long-term culture (Reproduced from Ref[76] with permission from the Royal Society of Chemistry); B: A miniaturized 96 well-type human iPSC-derived cardiac organoid (hCOs) screening platform, which is called heart dynamometer (Heart-Dyno), facilitates the automated formation of hCOs (Reproduced from Ref[86] with permission from the National Academy of Science); C: Well plate-micropattern hybrid platform for NPC differentiation for modeling Alzheimer’s disease (Reproduced from Ref[71] with permission form the Royal Society of Chemistry). This hybrid-platform is compatible with high-throughput screeninganalysis; D: Organo-plate® comprising 96 microfluidic tissue chips and experimental outline for culturing 3D neuronal-glial networks (reproduced from Ref[94] with permission from the Nature Research).