Park, JiSoo Lee, Bo Kyeong Jeong, Gi Seok Hyun, Jung Keun Lee, C. Justin Lee, Sang-Hoon 2024-01-20T08:02:19Z 2024-01-20T08:02:19Z 2021-09-05 2015-01 1473-0197 https://pubs.kist.re.kr/handle/201004/125912 There has been a growing need for in vitro models of neurodegenerative diseases such as Alzheimer's disease that would enable a better understanding of etiology and faster development of treatment strategies. However, meeting this demand has been held back by the limited ability to mimic the in vivo microenvironment in an in vitro system. Here, we developed a microfluidic chip based on three-dimensional (3D) neurospheroids that more closely mimics the in vivo brain microenvironment by providing a constant flow of fluid that is readily observed in the interstitial space of the brain. Uniform neurospheroids, with cell-cell interactions and contacts in all directions, were formed in concave microwell arrays, and a slow interstitial level of flow was maintained using an osmotic micropump system. Using this platform, we investigated the effect of flow on neurospheroid size, neural network, and neural differentiation. Neurospheroids cultured with flow were larger and formed more robust and complex neural networks than those cultured under static conditions, suggesting an effect of the interstitial level of slow and diffusion-dominant flow on continuous nutrient, oxygen, and cytokine transport and removal of metabolic wastes. We also tested the toxic effects of amyloid-beta, which is generally considered to be the major contributor in Alzheimer's disease. Amyloid-beta treatment via an osmotic micropump significantly reduced the viability of neurospheroids and caused a significantly more destruction of neural networks, compared to the amyloid-beta treatment under static conditions. By adding in vivo-like microenvironments, we propose this 3D culture-based microfluidic chip as an in vitro brain model for neurodegenerative disease and high-throughput drug screening. English Royal Society of Chemistry CONCAVE-MICROWELL ARRAYS MESENCHYMAL STEM-CELLS EMBRYOID BODIES CULTURE-SYSTEM TISSUE DIFFERENTIATION 3RD-DIMENSION GENERATION PEPTIDE NEURONS Three-dimensional brain-on-a-chip with an interstitial level of flow and its application as an in vitro model of Alzheimer's disease Article 10.1039/c4lc00962b 1 Lab on a Chip, v.15, no.1, pp.141 - 150 Lab on a Chip 15 1 141 150 scie scopus 000346478100018 2-s2.0-84915821053 Biochemical Research Methods Chemistry, Multidisciplinary Chemistry, Analytical Nanoscience & Nanotechnology Instruments & Instrumentation Biochemistry & Molecular Biology Chemistry Science & Technology - Other Topics Instruments & Instrumentation Article CONCAVE-MICROWELL ARRAYS MESENCHYMAL STEM-CELLS EMBRYOID BODIES CULTURE-SYSTEM TISSUE DIFFERENTIATION 3RD-DIMENSION GENERATION PEPTIDE NEURONS