Recent Advances in 3D-Cultured Brain Tissue Models Derived from Human iPSCs

Neurological diseases are caused by defects in the brain, spinal cord, or nervous system. Excluding animal models, ex vivo brain tissues and brain organoids have been used for modeling neurological diseases. In addition, the blood-brain barrier (BBB) is a selective semipermeable membrane that separates the peripheral blood from the neural tissue. Thus, it regulates homeostasis of the brain and selectively delivers substances essential for brain function. The property of the BBB can often be a double-edged sword by impeding the penetration of therapeutic drugs for brain diseases. Dysregulation of the BBB can lead to various neurological diseases. To date, significant efforts have been made to develop human brain organoids and BBB models with pluripotent stem cells for mimicking neurological diseases. Since human ex vivo brain tissues are difficult to obtain from a patient directly, induced pluripotent stem cells (iPSCs) generated by genetic reprogramming of adult somatic cells have been differentiated into specific neural cell types or brain organoids. Conventionally, major brain cell types including neurons, oligodendrocytes, and astrocytes have been generated from iPSCs in two-dimensional (2D) monolayer culture plates, whereas brain organoids have been differentiated in three-dimensional (3D) culture systems. Region-specific brain organoids become an important tool to study biological mechanisms of neurological disorders. Nonetheless, brain organoids generated in static conditions show several challenges in culture, which include diffusion limitation of nutrients and oxygen and removal of metabolic waste. To resolve these issues, microfluidic chip systems have been adopted for brain organoid culture and facilitate disease modeling and precision medicine. In this short review, we summarize recent advances in brain organoid culture with iPSCs and brain organoid-on-a-chip.