TY - JOUR
T1 - Organ-On-A-Chip in vitro Models of the Brain and the Blood-Brain Barrier and Their Value to Study the Microbiota-Gut-Brain Axis in Neurodegeneration
AU - Raimondi, Ilaria
AU - Izzo, Luca
AU - Tunesi, Marta
AU - Comar, Manola
AU - Albani, Diego
AU - Giordano, Carmen
N1 - Funding Information: MINERVA project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant Agreement no. 724734). Publisher Copyright: © Copyright © 2020 Raimondi, Izzo, Tunesi, Comar, Albani and Giordano. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
M1 - 435
PY - 2020/1/10
Y1 - 2020/1/10
N2 - We are accumulating evidence that intestinal microflora, collectively named gut microbiota, can alter brain pathophysiology, but researchers have just begun to discover the mechanisms of this bidirectional connection (often referred to as microbiota-gut-brain axis, MGBA). The most noticeable hypothesis for a pathological action of gut microbiota on the brain is based on microbial release of soluble neurotransmitters, hormones, immune molecules and neuroactive metabolites, but this complex scenario requires reliable and controllable tools for its causal demonstration. Thanks to three-dimensional (3D) cultures and microfluidics, engineered in vitro models could improve the scientific knowledge in this field, also from a therapeutic perspective. This review briefly retraces the main discoveries linking the activity of gut microbiota to prevalent brain neurodegenerative disorders, and then provides a deep insight into the state-of-the-art for in vitro modeling of the brain and the blood-brain barrier (BBB), two key players of the MGBA. Several brain and BBB microfluidic devices have already been developed to implement organ-on-a-chip solutions, but some limitations still exist. Future developments of organ-on-a-chip tools to model the MGBA will require an interdisciplinary approach and the synergy with cutting-edge technologies (for instance, bioprinting) to achieve multi-organ platforms and support basic research, also for the development of new therapies against neurodegenerative diseases.
AB - We are accumulating evidence that intestinal microflora, collectively named gut microbiota, can alter brain pathophysiology, but researchers have just begun to discover the mechanisms of this bidirectional connection (often referred to as microbiota-gut-brain axis, MGBA). The most noticeable hypothesis for a pathological action of gut microbiota on the brain is based on microbial release of soluble neurotransmitters, hormones, immune molecules and neuroactive metabolites, but this complex scenario requires reliable and controllable tools for its causal demonstration. Thanks to three-dimensional (3D) cultures and microfluidics, engineered in vitro models could improve the scientific knowledge in this field, also from a therapeutic perspective. This review briefly retraces the main discoveries linking the activity of gut microbiota to prevalent brain neurodegenerative disorders, and then provides a deep insight into the state-of-the-art for in vitro modeling of the brain and the blood-brain barrier (BBB), two key players of the MGBA. Several brain and BBB microfluidic devices have already been developed to implement organ-on-a-chip solutions, but some limitations still exist. Future developments of organ-on-a-chip tools to model the MGBA will require an interdisciplinary approach and the synergy with cutting-edge technologies (for instance, bioprinting) to achieve multi-organ platforms and support basic research, also for the development of new therapies against neurodegenerative diseases.
KW - blood-brain barrier
KW - brain
KW - in vitro modeling
KW - microbiota-gut-brain axis
KW - microfluidics
KW - neurodegenerative diseases
U2 - 10.3389/fbioe.2019.00435
DO - 10.3389/fbioe.2019.00435
M3 - Articolo
VL - 7
SP - 435
JO - Frontiers in Bioengineering and Biotechnology
JF - Frontiers in Bioengineering and Biotechnology
SN - 2296-4185
ER -