Bioengineering of a human physiologically relevant microfluidic blood–cerebrospinal fluid barrier model

Zhou, Ying; Qiao, Haowen; Xu, Fang; Zhao, Wenjing; Wang, Jibo; Gu, Longjun; Chen, Pu; Peng, Mian

doi:10.1039/d3lc00131h

Cited by 6 publications

(6 citation statements)

References 48 publications

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“…Integrating vascularization within brain organoids could mitigate the issue of nutrient accessibility and support the development of more physiologically relevant models [ 144 ]. By integrating the CSF on microfluidic devices, the human blood–cerebrospinal fluid barrier (hBCSFB) could be modeled to study neuroinflammation-related diseases by simulating the neuropathological conditions [ 203 ]. Additionally, high-throughput organs-on-a-chip systems incorporating automatic analytic tools and complicated designs for co-culturing multiple organs need to be more advanced to improve throughput and reduce errors caused by experiment operations between batches.…”

Section: Discussionmentioning

confidence: 99%

Human Brain In Vitro Model for Pathogen Infection-Related Neurodegeneration Study

Yan,

Cho

2024

IJMS

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Recent advancements in stem cell biology and tissue engineering have revolutionized the field of neurodegeneration research by enabling the development of sophisticated in vitro human brain models. These models, including 2D monolayer cultures, 3D organoids, organ-on-chips, and bioengineered 3D tissue models, aim to recapitulate the cellular diversity, structural organization, and functional properties of the native human brain. This review highlights how these in vitro brain models have been used to investigate the effects of various pathogens, including viruses, bacteria, fungi, and parasites infection, particularly in the human brain cand their subsequent impacts on neurodegenerative diseases. Traditional studies have demonstrated the susceptibility of different 2D brain cell types to infection, elucidated the mechanisms underlying pathogen-induced neuroinflammation, and identified potential therapeutic targets. Therefore, current methodological improvement brought the technology of 3D models to overcome the challenges of 2D cells, such as the limited cellular diversity, incomplete microenvironment, and lack of morphological structures by highlighting the need for further technological advancements. This review underscored the significance of in vitro human brain cell from 2D monolayer to bioengineered 3D tissue model for elucidating the intricate dynamics for pathogen infection modeling. These in vitro human brain cell enabled researchers to unravel human specific mechanisms underlying various pathogen infections such as SARS-CoV-2 to alter blood-brain-barrier function and Toxoplasma gondii impacting neural cell morphology and its function. Ultimately, these in vitro human brain models hold promise as personalized platforms for development of drug compound, gene therapy, and vaccine. Overall, we discussed the recent progress in in vitro human brain models, their applications in studying pathogen infection-related neurodegeneration, and future directions.

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Section: Discussionmentioning

confidence: 99%

Human Brain In Vitro Model for Pathogen Infection-Related Neurodegeneration Study

Yan,

Cho

2024

IJMS

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“…The microfluidic approach in the establishment of BCSFB in vitro models was introduced in 2023, when a previously developed standard chip geometry was used to create the dynamic BCSFB in vitro model. 225 The main advantages of the model are the co-culture of human CPECs and BMECs and the application of shear stress. Barrier properties, including modeling of neuroinflammation (TNF-treated cells), were assessed by immunofluorescence imaging, permeability measurements and transcriptional profiling of epithelial cells.…”

Section: Development Of a Changeable Brain: 4d Neurogenic Niche In Vi...mentioning

confidence: 99%

“…The indications of the most typical in vitro BBB and BCSFB models and their main parameters are given on the chronological axis. 190 – 192 , 194 , 195 , 197 , 200 , 205 , 214 , 222 , 225 , 232 , 233 …”

Section: Development Of a Changeable Brain: 4d Neurogenic Niche In Vi...mentioning

confidence: 99%

Current progress and challenges in the development of brain tissue models: How to grow up the changeable brain in vitro?

Salmina,

Alexandrova,

Averchuk

et al. 2024

J Tissue Eng

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In vitro modeling of brain tissue is a promising but not yet resolved problem in modern neurobiology and neuropharmacology. Complexity of the brain structure and diversity of cell-to-cell communication in (patho)physiological conditions make this task almost unachievable. However, establishment of novel in vitro brain models would ultimately lead to better understanding of development-associated or experience-driven brain plasticity, designing efficient approaches to restore aberrant brain functioning. The main goal of this review is to summarize the available data on methodological approaches that are currently in use, and to identify the most prospective trends in development of neurovascular unit, blood-brain barrier, blood-cerebrospinal fluid barrier, and neurogenic niche in vitro models. The manuscript focuses on the regulation of adult neurogenesis, cerebral microcirculation and fluids dynamics that should be reproduced in the in vitro 4D models to mimic brain development and its alterations in brain pathology. We discuss approaches that are critical for studying brain plasticity, deciphering the individual person-specific trajectory of brain development and aging, and testing new drug candidates in the in vitro models.

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“…For example, a study conducted by Zhou et al designed a blood–cerebrospinal fluid barrier microfluidic model that allowed two parallel and opposed microchannels separated by a polyester porous membrane to be continuously perfused. This allowed for the monitoring of mass transport and diffusion of molecules from each channel paving the way for further analysis into essential neuroimmune interactions within the blood–cerebrospinal barrier [ 221 ]. Similarly, a study published by Brown et al employed a two-chamber system divided by a polycarbonate membrane made from polydimethylsiloxane (PDMS) and seeded different cell types in opposition to form their neurovascular blood brain barrier unit [ 222 ].…”

Section: In Vitro and Preclinical Studies For Alzheimer’s And Parkins...mentioning

confidence: 99%

Modeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases

Balestri,

Sharma,

da Silva

et al. 2024

J Neuroinflammation

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Parkinson’s disease (PD) and Alzheimer’s disease (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, and familial factors. These diseases have distinct pathologies and symptoms that are linked to specific cell populations in the brain. Notably, the immune system has been implicated in both diseases, with a particular focus on the dysfunction of microglia, the brain’s resident immune cells, contributing to neuronal loss and exacerbating symptoms. Researchers use models of the neuroimmune system to gain a deeper understanding of the physiological and biological aspects of these neurodegenerative diseases and how they progress. Several in vitro and in vivo models, including 2D cultures and animal models, have been utilized. Recently, advancements have been made in optimizing these existing models and developing 3D models and organ-on-a-chip systems, holding tremendous promise in accurately mimicking the intricate intracellular environment. As a result, these models represent a crucial breakthrough in the transformation of current treatments for PD and AD by offering potential for conducting long-term disease-based modeling for therapeutic testing, reducing reliance on animal models, and significantly improving cell viability compared to conventional 2D models. The application of 3D and organ-on-a-chip models in neurodegenerative disease research marks a prosperous step forward, providing a more realistic representation of the complex interactions within the neuroimmune system. Ultimately, these refined models of the neuroimmune system aim to aid in the quest to combat and mitigate the impact of debilitating neuroimmune diseases on patients and their families.

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Bioengineering of a human physiologically relevant microfluidic blood–cerebrospinal fluid barrier model

Abstract: The human blood-cerebrospinal fluid barrier (hBCSFB) plays a crucial role in regulating brain interstitial fluid homeostasis, and disruption of the hBCSFB is associated with various neurological diseases. Generation of the...

Cited by 6 publications

References 48 publications

Human Brain In Vitro Model for Pathogen Infection-Related Neurodegeneration Study

Human Brain In Vitro Model for Pathogen Infection-Related Neurodegeneration Study

Current progress and challenges in the development of brain tissue models: How to grow up the changeable brain in vitro?

Modeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases

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