scholarly journals Recapitulating the Vasculature Using Organ-On-Chip Technology

2020 ◽  
Vol 7 (1) ◽  
pp. 17 ◽  
Author(s):  
Andreas M.A.O. Pollet ◽  
Jaap M.J. den Toonder
Keyword(s):  
Advantages And Disadvantages ◽  
Biological Relevance ◽  
Chip Technology ◽  
Intrinsic Complexity ◽  
On Chip

The development of Vasculature-on-Chip has progressed rapidly over the last decade and recently, a wealth of fabrication possibilities has emerged that can be used for engineering vessels on a chip. All these fabrication methods have their own advantages and disadvantages but, more importantly, the capability of recapitulating the in vivo vasculature differs greatly between them. The first part of this review discusses the biological background of the in vivo vasculature and all the associated processes. We then evaluate the biological relevance of different fabrication methods proposed for Vasculature-on-Chip, we indicate their possibilities and limitations, and we assess which fabrication methods are capable of recapitulating the intrinsic complexity of the vasculature. This review illustrates the complexity involved in developing in vitro vasculature and provides an overview of fabrication methods for Vasculature-on-Chip in relation to the biological relevance of such methods.

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 Microengineered Lung Models for Translational Drug Discovery

2018 ◽  
Vol 23 (8) ◽  
pp. 777-789 ◽  
Author(s):  
Brian F. Niemeyer ◽  
Peng Zhao ◽  
Rubin M. Tuder ◽  
Kambez H. Benam
Keyword(s):  
Biomarker Discovery ◽  
Human Lung ◽  
In Vivo Models ◽  
Chip Technology ◽  
Preclinical Drug Development ◽  
Lung Alveolus ◽  
Organ Level ◽  
On Chip

Lung diseases impose a significant socioeconomic burden and are a leading cause of morbidity and mortality worldwide. Moreover, respiratory medicine, unlike several other therapeutic areas, faces a disappointingly low number of new approved therapies. This is partly due to lack of reliable in vitro or in vivo models that can reproduce organ-level complexity and pathophysiological responses of human lung. Here, we examine new opportunities in application of recently emerged organ-on-chip technology to model human lung alveolus and small airway in preclinical drug development and biomarker discovery. We also discuss challenges that need to be addressed in coming years to further enhance the physiological and clinical relevance of these microsystems, enable their increased accessibility, and support their leap into personalized medicine.

scholarly journals Immunotherapy-on-chip Against an Experimental Sepsis Model

2021 ◽  
Author(s):  
Ioanna Zerva ◽  
Katerina Bakela ◽  
Irene Athanassakis
Keyword(s):  
Micrococcus Luteus ◽  
Experimental Sepsis ◽  
Immunostimulatory Activity ◽  
Cd8 Cells ◽  
Arginase 1 ◽  
Chip Technology ◽  
On Chip ◽  
Lps Treatment

Abstract Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the protective role of Micrococcus luteus peptidoglycan (PG) pre-activated vaccine-on chip technology in endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2mg/g LPS, allowing longer survival, necessary for a therapeutic treatment application. A novel immunotherapy technology, the so-called vaccine-on-chip consists of a 3-dimentional laser micro-textured silicon (Si)-scaffold loaded with macrophages and activated in vitro with 1μg/ml PG, which has been previously shown to exert a mild immunostimulatory activity upon subcutaneous implantation. The LPS treatment significantly decreased CD4+ and CD8+ cells, while increasing CD11b+, Gr1+, CD25+, Foxp3+ and class II+ cells. These results were accompanied by increased arginase-1 activity in spleen cell lysates and C-reactive protein (CRP), procalcitonin (PCT), IL-6, TNF-a, IL-10 and IL-18 in the serum, while acquiring severe sepsis phenotype as defined by the murine sepsis scoring. The in vivo application of PG pre-activated implant significantly increased the percentage of CD4+ and CD8+ cells, while decreasing the percentage of Gr1+, CD25+, CD11b+, Foxp3+ cells and arginase-1 activity in the spleen of LPS-treated animals, as well as all serum markers tested, allowing survival and rescuing the severity of sepsis phenotype. In conclusion, these results reveal a novel immunotherapy technology based on PG pre-activated micro-texture Si-scaffolds in LPS endotoxemia, supporting thus its potential use in the treatment of septic patients.

scholarly journals Technological Advances in Tumor-On-Chip Technology: From Bench to Bedside

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4192
Author(s):  
Santa Bērziņa ◽  
Alexandra Harrison ◽  
Valérie Taly ◽  
Wenjin Xiao
Keyword(s):  
Tumor Model ◽  
Cancer Therapies ◽  
Analysis Tools ◽  
Chip Technology ◽  
Technological Advances ◽  
Anti Cancer ◽  
On Chip ◽  
Chip Analysis

Tumor-on-chip technology has cemented its importance as an in vitro tumor model for cancer research. Its ability to recapitulate different elements of the in vivo tumor microenvironment makes it promising for translational medicine, with potential application in enabling personalized anti-cancer therapies. Here, we provide an overview of the current technological advances for tumor-on-chip generation. To further elevate the functionalities of the technology, these approaches need to be coupled with effective analysis tools. This aspect of tumor-on-chip technology is often neglected in the current literature. We address this shortcoming by reviewing state-of-the-art on-chip analysis tools for microfluidic tumor models. Lastly, we focus on the current progress in tumor-on-chip devices using patient-derived samples and evaluate their potential for clinical research and personalized medicine applications.

PERFUSION OF OVARIES IN VITRO AND IN VIVO

1972 ◽  
Vol 68 (2_Supplb) ◽  
pp. S285-S309 ◽  
Author(s):  
Kurt Ahrén ◽  
Per Olof Janson ◽  
Gunnar Selstam
Keyword(s):  
Perfusion System ◽  
Perfusion Technique ◽  
Preliminary Results ◽  
Advantages And Disadvantages

ABSTRACT This paper discusses in vivo and in vitro ovarian perfusion systems described so far in the literature. The interest is not focussed primarily on the results of these studies but rather on the advantages and disadvantages of the techniques and methods used. Another part of the paper summarizes the points which are most important, in our opinion, to take into consideration when developing an in vitro perfusion technique of the ovary. The last part of the paper gives a description of and some preliminary results from an in vitro perfusion system of the rabbit ovary which is under development in this laboratory.

scholarly journals Transcriptome comparisons of in vitro intestinal epithelia grown under static and microfluidic gut-on-chip conditions with in vivo human epithelia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kornphimol Kulthong ◽  
Guido J. E. J. Hooiveld ◽  
Loes Duivenvoorde ◽  
Ignacio Miro Estruch ◽  
Victor Marin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Culture Conditions ◽  
Gene Set Enrichment Analysis ◽  
Shear Stresses ◽  
Static Culture ◽  
Dynamic Culture ◽  
Intestinal Segments ◽  
On Chip

AbstractGut-on-chip devices enable exposure of cells to a continuous flow of culture medium, inducing shear stresses and could thus better recapitulate the in vivo human intestinal environment in an in vitro epithelial model compared to static culture methods. We aimed to study if dynamic culture conditions affect the gene expression of Caco-2 cells cultured statically or dynamically in a gut-on-chip device and how these gene expression patterns compared to that of intestinal segments in vivo. For this we applied whole genome transcriptomics. Dynamic culture conditions led to a total of 5927 differentially expressed genes (3280 upregulated and 2647 downregulated genes) compared to static culture conditions. Gene set enrichment analysis revealed upregulated pathways associated with the immune system, signal transduction and cell growth and death, and downregulated pathways associated with drug metabolism, compound digestion and absorption under dynamic culture conditions. Comparison of the in vitro gene expression data with transcriptome profiles of human in vivo duodenum, jejunum, ileum and colon tissue samples showed similarities in gene expression profiles with intestinal segments. It is concluded that both the static and the dynamic gut-on-chip model are suitable to study human intestinal epithelial responses as an alternative for animal models.

scholarly journals Role of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 914
Author(s):  
Melanie V. Brady ◽  
Flora M. Vaccarino
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Human Development ◽  
Disease Modeling ◽  
Model Systems ◽  
Advantages And Disadvantages ◽  
Technical Ability ◽  
Cellular Phenotypes

The complexities of human neurodevelopment have historically been challenging to decipher but continue to be of great interest in the contexts of healthy neurobiology and disease. The classic animal models and monolayer in vitro systems have limited the types of questions scientists can strive to answer in addition to the technical ability to answer them. However, the tridimensional human stem cell-derived organoid system provides the unique opportunity to model human development and mimic the diverse cellular composition of human organs. This strategy is adaptable and malleable, and these neural organoids possess the morphogenic sensitivity to be patterned in various ways to generate the different regions of the human brain. Furthermore, recapitulating human development provides a platform for disease modeling. One master regulator of human neurodevelopment in many regions of the human brain is sonic hedgehog (SHH), whose expression gradient and pathway activation are responsible for conferring ventral identity and shaping cellular phenotypes throughout the neural axis. This review first discusses the benefits, challenges, and limitations of using organoids for studying human neurodevelopment and disease, comparing advantages and disadvantages with other in vivo and in vitro model systems. Next, we explore the range of control that SHH exhibits on human neurodevelopment, and the application of SHH to various stem cell methodologies, including organoids, to expand our understanding of human development and disease. We outline how this strategy will eventually bring us much closer to uncovering the intricacies of human neurodevelopment and biology.

scholarly journals CTCF Interacts with and Recruits the Largest Subunit of RNA Polymerase II to CTCF Target Sites Genome-Wide

2007 ◽  
Vol 27 (5) ◽  
pp. 1631-1648 ◽  
Author(s):  
Igor Chernukhin ◽  
Shaharum Shamsuddin ◽  
Sung Yun Kang ◽  
Rosita Bergström ◽  
Yoo-Wook Kwon ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Gene Activation ◽  
Ctcf Binding ◽  
Pol Ii ◽  
Genome Wide ◽  
Target Sites ◽  
On Chip

ABSTRACT CTCF is a transcription factor with highly versatile functions ranging from gene activation and repression to the regulation of insulator function and imprinting. Although many of these functions rely on CTCF-DNA interactions, it is an emerging realization that CTCF-dependent molecular processes involve CTCF interactions with other proteins. In this study, we report the association of a subpopulation of CTCF with the RNA polymerase II (Pol II) protein complex. We identified the largest subunit of Pol II (LS Pol II) as a protein significantly colocalizing with CTCF in the nucleus and specifically interacting with CTCF in vivo and in vitro. The role of CTCF as a link between DNA and LS Pol II has been reinforced by the observation that the association of LS Pol II with CTCF target sites in vivo depends on intact CTCF binding sequences. “Serial” chromatin immunoprecipitation (ChIP) analysis revealed that both CTCF and LS Pol II were present at the β-globin insulator in proliferating HD3 cells but not in differentiated globin synthesizing HD3 cells. Further, a single wild-type CTCF target site (N-Myc-CTCF), but not the mutant site deficient for CTCF binding, was sufficient to activate the transcription from the promoterless reporter gene in stably transfected cells. Finally, a ChIP-on-ChIP hybridization assay using microarrays of a library of CTCF target sites revealed that many intergenic CTCF target sequences interacted with both CTCF and LS Pol II. We discuss the possible implications of our observations with respect to plausible mechanisms of transcriptional regulation via a CTCF-mediated direct link of LS Pol II to the DNA.

The Role of Microbiology in Models of Dental Caries: Reaction Paper

1995 ◽  
Vol 9 (3) ◽  
pp. 255-269 ◽  
Author(s):  
G.H. Bowden
Keyword(s):  
Process Selection ◽  
Advantages And Disadvantages ◽  
Test Models ◽  
Plaque Development ◽  
In Vitro Systems ◽  
Selection Of

Models of the caries process have made significant contributions toward defining the roles of bacteria in caries. Microbiologists use a variety of in vitro systems to model aspects of the caries process. Also, in situ models in humans provide information on the microbiology of caries in vivo. These models do not involve the entire process leading to natural caries; consequently, the results from such studies are used to deduce the roles of bacteria in natural caries. Therefore, they can be described as Inferential Caries Models. In contrast, animal models and some clinical trials in humans involve natural caries and can be described as Complete Caries Models. Furthermore, these models are used in two distinct ways. They can be used as Exploratory Models to explore different aspects of the caries process, or as Test Models to determine the effects of anticaries agents. This dichotomy in approach to the use of caries models results in modification of the models to suit a particular role. For example, if we consider Exploratory Models, the in situ appliance in humans is superior to others for analyzing the microbiology of plaque development and demineralization in vivo. The chemostat and biofilm models are excellent for exploring factors influencing bacterial interactions. Both models can also be used as Test Models. The in situ model has been used to test the effects of fluoride on the microflora and demineralization, while the chemostat and biofilm models allow for the testing of antibacterial agents. Each model has its advantages and disadvantages and role in analysis of the caries process. Selection of the model depends on the scientific question posed and the limitations imposed by the conditions available for the study.

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
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