scholarly journals Dynamic 3D On-Chip BBB Model Design, Development, and Applications in Neurological Diseases

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3183
Author(s):  
Xingchi Chen ◽  
Chang Liu ◽  
Laureana Muok ◽  
Changchun Zeng ◽  
Yan Li
Keyword(s):  
Targeted Delivery ◽  
Neurological Diseases ◽  
In Vitro Models ◽  
Normal Function ◽  
Human Stem Cells ◽  
Design Development ◽  
High Throughput Drug Screening ◽  
The Central Nervous System ◽  
On Chip

The blood–brain barrier (BBB) is a vital structure for maintaining homeostasis between the blood and the brain in the central nervous system (CNS). Biomolecule exchange, ion balance, nutrition delivery, and toxic molecule prevention rely on the normal function of the BBB. The dysfunction and the dysregulation of the BBB leads to the progression of neurological disorders and neurodegeneration. Therefore, in vitro BBB models can facilitate the investigation for proper therapies. As the demand increases, it is urgent to develop a more efficient and more physiologically relevant BBB model. In this review, the development of the microfluidics platform for the applications in neuroscience is summarized. This article focuses on the characterizations of in vitro BBB models derived from human stem cells and discusses the development of various types of in vitro models. The microfluidics-based system and BBB-on-chip models should provide a better platform for high-throughput drug-screening and targeted delivery.

scholarly journals Effects of Platelet-Rich Plasma on Cellular Populations of the Central Nervous System: The Influence of Donor Age

2021 ◽  
Vol 22 (4) ◽  
pp. 1725
Author(s):  
Diego Delgado ◽  
Ane Miren Bilbao ◽  
Maider Beitia ◽  
Ane Garate ◽  
Pello Sánchez ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cellular Response ◽  
Platelet Rich Plasma ◽  
Biological Response ◽  
In Vitro Models ◽  
Molecular Composition ◽  
Cellular Models ◽  
The Central Nervous System

Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor’s health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the differences between PRP from young and elderly donors. Two different PRP pools were prepared from donors 65–85 and 20–25 years old. The cellular and molecular composition of both PRPs were analyzed. Subsequently, the cellular response was evaluated in CNS in vitro models, studying proliferation, neurogenesis, synaptogenesis, and inflammation. While no differences in the cellular composition of PRPs were found, the molecular composition of the Young PRP showed lower levels of inflammatory molecules such as CCL-11, as well as the presence of other factors not found in Aged PRP (GDF-11). Although both PRPs had effects in terms of reducing neural progenitor cell apoptosis, stabilizing neuronal synapses, and decreasing inflammation in the microglia, the effect of the Young PRP was more pronounced. In conclusion, the molecular composition of the PRP, conditioned by the age of the donors, affects the magnitude of the biological response.

scholarly journals New Endeavors of (Micro)Tissue Engineering: Cells Tissues Organs on-Chip and Communication Thereof

2021 ◽  
pp. 1-15
Author(s):  
Haysam M.M.A.M. Ahmed ◽  
Liliana S. Moreira Teixeira
Keyword(s):  
Tissue Engineering ◽  
Food Additives ◽  
Market Potential ◽  
Model Systems ◽  
Human Model ◽  
Human Stem Cells ◽  
Animal Testing ◽  
Preclinical Research ◽  
On Chip

The development of new therapies is tremendously hampered by the insufficient availability of human model systems suitable for preclinical research on disease target identification, drug efficacy, and toxicity. Thus, drug failures in clinical trials are too common and too costly. Animal models or standard 2D in vitro tissue cultures, regardless of whether they are human based, are regularly not representative of specific human responses. Approaching near human tissues and organs test systems is the key goal of organs-on-chips (OoC) technology. This technology is currently showing its potential to reduce both drug development costs and time-to-market, while critically lessening animal testing. OoC are based on human (stem) cells, potentially derived from healthy or disease-affected patients, thereby amenable to personalized therapy development. It is noteworthy that the OoC market potential goes beyond pharma, with the possibility to test cosmetics, food additives, or environmental contaminants. This (micro)tissue engineering-based technology is highly multidisciplinary, combining fields such as (developmental) biology, (bio)materials, microfluidics, sensors, and imaging. The enormous potential of OoC is currently facing an exciting new challenge: emulating cross-communication between tissues and organs, to simulate more complex systemic responses, such as in cancer, or restricted to confined environments, as occurs in osteoarthritis. This review describes key examples of multiorgan/tissue-on-chip approaches, or linked organs/tissues-on-chip, focusing on challenges and promising new avenues of this advanced model system. Additionally, major emphasis is given to the translation of established tissue engineering approaches, bottom up and top down, towards the development of more complex, robust, and representative (multi)organ/tissue-on-chip approaches.

Overview of existing in vitro BBB models: advantages and disadvantages, current state and future prospects

2021 ◽  
Vol 10 (3) ◽  
pp. 109-120
Author(s):  
A. I. Mosiagina ◽  
A. V. Morgun ◽  
A. B. Salmina
Keyword(s):  
Neurovascular Unit ◽  
Clinical Trial Data ◽  
Advantages And Disadvantages ◽  
The Central Nervous System ◽  
Complex Relationships ◽  
On Chip ◽  
Induced Pluripotent ◽  
Level Of Understanding

There is growing research focusing on endothelial cells as separate units of the blood-brain barrier (BBB), and on the complex relationships between different types of cells within a neurovascular unit. To conduct this type of studies, researches use vastly different in vitro BBB models. The main objective of such models is to study the BBB permeability for different molecules, and to advance the current level of understanding the mechanisms of disease and to develop methods of targeted therapy for the central nervous system. The analysis of the existing Abstract in vitro BBB models and their advantages/disadvantages was conducted using the clinical trial data obtained in Russian/foreign countries. In this review, the authors highlight the most relevant assessment parameters and propose a unified classification of in vitro BBB models. According to the performed analysis, there is a tendency to move from 2D BBB models based on semipermeable inserts to 3D BBB spheroid and microfluidic organ-on-chip models. Moreover, the use of human induced pluripotent stem cells instead of animal primary cells will make it possible to reliably scale the results obtained in vitro to conditions in vivo.

scholarly journals Advanced in vitro models of vascular biology: Human induced pluripotent stem cells and organ-on-chip technology

2019 ◽  
Vol 140 ◽  
pp. 68-77 ◽  
Author(s):  
Amy Cochrane ◽  
Hugo J. Albers ◽  
Robert Passier ◽  
Christine L. Mummery ◽  
Albert van den Berg ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Vascular Biology ◽  
In Vitro Models ◽  
Chip Technology ◽  
On Chip ◽  
Induced Pluripotent

scholarly journals Enhanced Virulence Mediated by the Murine Coronavirus, Mouse Hepatitis Virus Strain JHM, Is Associated with a Glycine at Residue 310 of the Spike Glycoprotein

2003 ◽  
Vol 77 (19) ◽  
pp. 10260-10269 ◽  
Author(s):  
Evelena Ontiveros ◽  
Taeg S. Kim ◽  
Thomas M. Gallagher ◽  
Stanley Perlman
Keyword(s):  
Virus Strain ◽  
Hepatitis Virus ◽  
Neurological Diseases ◽  
Mouse Hepatitis Virus ◽  
Neutralizing Antibody ◽  
Lateral Spread ◽  
S Protein ◽  
Acute Encephalitis ◽  
The Central Nervous System

ABSTRACT The coronavirus, mouse hepatitis virus strain JHM, causes acute and chronic neurological diseases in rodents. Here we demonstrate that two closely related virus variants, both of which cause acute encephalitis in susceptible strains of mice, cause markedly different diseases if mice are protected with a suboptimal amount of an anti-JHM neutralizing antibody. One strain, JHM.SD, caused acute encephalitis, while infection with JHM.IA resulted in no acute disease. Using recombinant virus technology, we found that the differences between the two viruses mapped to the spike (S) glycoprotein and that the two S proteins differed at four amino acids. By engineering viruses that differed by only one amino acid, we identified a serine-to-glycine change at position 310 of the S protein (S310G) that recapitulated the more neurovirulent phenotype. The increased neurovirulence mediated by the virus encoding glycine at position S310 was not associated with a different tropism within the central nervous system (CNS) but was associated with increased lateral spread in the CNS, leading to significantly higher brain viral titers. In vitro studies revealed that S310G was associated with decreased S1-S2 stability and with enhanced ability to mediate infection of cells lacking the primary receptor for JHM (“receptor-independent spread”). These enhanced fusogenic properties of viruses encoding a glycine at position 310 of the S protein may contribute to spread within the CNS, a tissue in which expression of conventional JHM receptors is low.

scholarly journals Laser Recording of Subcellular Neuron Activities

2019 ◽  
Author(s):  
Yu-Cheng Chen ◽  
Xuzhou Li ◽  
Hongbo Zhu ◽  
Wei-Hung Weng ◽  
Xiaotian Tan ◽  
...  
Keyword(s):  
Neuronal Networks ◽  
Signal To Noise Ratio ◽  
Neurological Diseases ◽  
Detection Sensitivity ◽  
Neuron Network ◽  
Neural Activities ◽  
Single Spike ◽  
On Chip ◽  
Low Sensitivity

AbstractAdvances in imaging and recording of neural activities with a single neuron resolution have played a significant role in understanding neurological diseases in the past decade. Conventional methods relying on patch-clamp and electrodes are regarded as invasive, whereas fluorescence-based imaging tools are useful but still suffer from a low signal-to-noise ratio and low sensitivity. Here we developed a novel optical imaging and recording system by employing laser emissions to record the action potentials in single neurons and neuronal networks caused by subtle transients (Ca2+concentration) in primary neuronsin vitrowith a subcellular and single-spike resolution. By recording the laser emissions from neurons, we discovered that lasing emissions could be biologically modulated by intracellular activities and extracellular stimulation with >100-fold improvement in detection sensitivity over traditional fluorescence-based measurement. Finally, we showed that ultrasound can wirelessly activate neurons adsorbed with piezoelectric BaTiO3nanoparticles, in which the neuron laser emissions were modulated by ultrasound. Our findings show that ultrasound stimulation can significantly increase the lasing intensity and neuron network response. This work not only opens the door to laser emission recording of intracellular dynamics in neuronal networks but may provide an ultra-sensitive detection method for brain-on-chip applications, optogenetics, and neuro-analysis.

scholarly journals In vitro models of HIV-1 infection of the central nervous system

2020 ◽  
Vol 32 ◽  
pp. 5-11
Author(s):  
Celeste Faia ◽  
Karlie Plaisance-Bonstaff ◽  
Francesca Peruzzi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
In Vitro Models ◽  
The Central Nervous System ◽  
Hiv 1

scholarly journals Airway-On-A-Chip: Designs and Applications for Lung Repair and Disease

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1602
Author(s):  
Tanya J. Bennet ◽  
Avineet Randhawa ◽  
Jessica Hua ◽  
Karen C. Cheung
Keyword(s):  
In Vitro Models ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Characterization Methods ◽  
Composition And Structure ◽  
Challenges And Opportunities ◽  
On Chip ◽  
Respiratory Conditions

The lungs are affected by illnesses including asthma, chronic obstructive pulmonary disease, and infections such as influenza and SARS-CoV-2. Physiologically relevant models for respiratory conditions will be essential for new drug development. The composition and structure of the lung extracellular matrix (ECM) plays a major role in the function of the lung tissue and cells. Lung-on-chip models have been developed to address some of the limitations of current two-dimensional in vitro models. In this review, we describe various ECM substitutes utilized for modeling the respiratory system. We explore the application of lung-on-chip models to the study of cigarette smoke and electronic cigarette vapor. We discuss the challenges and opportunities related to model characterization with an emphasis on in situ characterization methods, both established and emerging. We discuss how further advancements in the field, through the incorporation of interstitial cells and ECM, have the potential to provide an effective tool for interrogating lung biology and disease, especially the mechanisms that involve the interstitial elements.

scholarly journals Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives

2021 ◽  
Vol 22 (12) ◽  
pp. 6442
Author(s):  
Aida Kouhi ◽  
Vyshnavi Pachipulusu ◽  
Talya Kapenstein ◽  
Peisheng Hu ◽  
Alan L. Epstein ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Neurological Diseases ◽  
High Specificity ◽  
Biochemical Properties ◽  
Antibody Engineering ◽  
Stage Of Development ◽  
The Central Nervous System ◽  
Underlying Mechanisms ◽  
The Brain

Due to their high specificity, monoclonal antibodies have been widely investigated for their application in drug delivery to the central nervous system (CNS) for the treatment of neurological diseases such as stroke, Alzheimer’s, and Parkinson’s disease. Research in the past few decades has revealed that one of the biggest challenges in the development of antibodies for drug delivery to the CNS is the presence of blood–brain barrier (BBB), which acts to restrict drug delivery and contributes to the limited uptake (0.1–0.2% of injected dose) of circulating antibodies into the brain. This article reviews the various methods currently used for antibody delivery to the CNS at the preclinical stage of development and the underlying mechanisms of BBB penetration. It also describes efforts to improve or modulate the physicochemical and biochemical properties of antibodies (e.g., charge, Fc receptor binding affinity, and target affinity), to adapt their pharmacokinetics (PK), and to influence their distribution and disposition into the brain. Finally, a distinction is made between approaches that seek to modify BBB permeability and those that use a physiological approach or antibody engineering to increase uptake in the CNS. Although there are currently inherent difficulties in developing safe and efficacious antibodies that will cross the BBB, the future prospects of brain-targeted delivery of antibody-based agents are believed to be excellent.

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