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The Need for Physiological Micro-Nanofluidic Systems of the Brain

In this article, we review brain-on-a-chip models and associated underlying technologies. Micro-nanofluidic systems of the brain can utilize the entire spectrum of organoid technology. Notably, there is an urgent clinical need for a physiologically relevant microfluidic platform that can mimic the b...

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Autores principales: Frimat, Jean-Philippe, Luttge, Regina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514106/
https://www.ncbi.nlm.nih.gov/pubmed/31134196
http://dx.doi.org/10.3389/fbioe.2019.00100
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author Frimat, Jean-Philippe
Luttge, Regina
author_facet Frimat, Jean-Philippe
Luttge, Regina
author_sort Frimat, Jean-Philippe
collection PubMed
description In this article, we review brain-on-a-chip models and associated underlying technologies. Micro-nanofluidic systems of the brain can utilize the entire spectrum of organoid technology. Notably, there is an urgent clinical need for a physiologically relevant microfluidic platform that can mimic the brain. Brain diseases affect millions of people worldwide, and this number will grow as the size of elderly population increases, thus making brain disease a serious public health problem. Brain disease modeling typically involves the use of in vivo rodent models, which is time consuming, resource intensive, and arguably unethical because many animals are required for a single study. Moreover, rodent models may not accurately predict human diseases, leading to erroneous results, thus rendering animal models poor predictors of human responses to treatment. Various clinical researchers have highlighted this issue, showing that initial physiological descriptions of animal models rarely encompass all the desired human features, including how closely the model captures what is observed in patients. Consequently, such animal models only mimic certain disease aspects, and they are often inadequate for studying how a certain molecule affects various aspects of a disease. Thus, there is a great need for the development of the brain-on-a-chip technology based on which a human brain model can be engineered by assembling cell lines to generate an organ-level model. To produce such a brain-on-a-chip device, selection of appropriate cells lines is critical because brain tissue consists of many different neuronal subtypes, including a plethora of supporting glial cell types. Additionally, cellular network bio-architecture significantly varies throughout different brain regions, forming complex structures and circuitries; this needs to be accounted for in the chip design process. Compartmentalized microenvironments can also be designed within the microphysiological cell culture system to fulfill advanced requirements of a given application. On-chip integration methods have already enabled advances in Parkinson's disease, Alzheimer's disease, and epilepsy modeling, which are discussed herein. In conclusion, for the brain model to be functional, combining engineered microsystems with stem cell (hiPSC) technology is specifically beneficial because hiPSCs can contribute to the complexity of tissue architecture based on their level of differentiation and thereby, biology itself.
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spelling pubmed-65141062019-05-27 The Need for Physiological Micro-Nanofluidic Systems of the Brain Frimat, Jean-Philippe Luttge, Regina Front Bioeng Biotechnol Bioengineering and Biotechnology In this article, we review brain-on-a-chip models and associated underlying technologies. Micro-nanofluidic systems of the brain can utilize the entire spectrum of organoid technology. Notably, there is an urgent clinical need for a physiologically relevant microfluidic platform that can mimic the brain. Brain diseases affect millions of people worldwide, and this number will grow as the size of elderly population increases, thus making brain disease a serious public health problem. Brain disease modeling typically involves the use of in vivo rodent models, which is time consuming, resource intensive, and arguably unethical because many animals are required for a single study. Moreover, rodent models may not accurately predict human diseases, leading to erroneous results, thus rendering animal models poor predictors of human responses to treatment. Various clinical researchers have highlighted this issue, showing that initial physiological descriptions of animal models rarely encompass all the desired human features, including how closely the model captures what is observed in patients. Consequently, such animal models only mimic certain disease aspects, and they are often inadequate for studying how a certain molecule affects various aspects of a disease. Thus, there is a great need for the development of the brain-on-a-chip technology based on which a human brain model can be engineered by assembling cell lines to generate an organ-level model. To produce such a brain-on-a-chip device, selection of appropriate cells lines is critical because brain tissue consists of many different neuronal subtypes, including a plethora of supporting glial cell types. Additionally, cellular network bio-architecture significantly varies throughout different brain regions, forming complex structures and circuitries; this needs to be accounted for in the chip design process. Compartmentalized microenvironments can also be designed within the microphysiological cell culture system to fulfill advanced requirements of a given application. On-chip integration methods have already enabled advances in Parkinson's disease, Alzheimer's disease, and epilepsy modeling, which are discussed herein. In conclusion, for the brain model to be functional, combining engineered microsystems with stem cell (hiPSC) technology is specifically beneficial because hiPSCs can contribute to the complexity of tissue architecture based on their level of differentiation and thereby, biology itself. Frontiers Media S.A. 2019-05-07 /pmc/articles/PMC6514106/ /pubmed/31134196 http://dx.doi.org/10.3389/fbioe.2019.00100 Text en Copyright © 2019 Frimat and Luttge. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Frimat, Jean-Philippe
Luttge, Regina
The Need for Physiological Micro-Nanofluidic Systems of the Brain
title The Need for Physiological Micro-Nanofluidic Systems of the Brain
title_full The Need for Physiological Micro-Nanofluidic Systems of the Brain
title_fullStr The Need for Physiological Micro-Nanofluidic Systems of the Brain
title_full_unstemmed The Need for Physiological Micro-Nanofluidic Systems of the Brain
title_short The Need for Physiological Micro-Nanofluidic Systems of the Brain
title_sort need for physiological micro-nanofluidic systems of the brain
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514106/
https://www.ncbi.nlm.nih.gov/pubmed/31134196
http://dx.doi.org/10.3389/fbioe.2019.00100
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