scholarly journals Endothelial Cells as Tools to Model Tissue Microenvironment in Hypoxia-Dependent Pathologies

2021 ◽  
Vol 22 (2) ◽  
pp. 520
Author(s):  
Aleksandra Majewska ◽  
Kinga Wilkus ◽  
Klaudia Brodaczewska ◽  
Claudine Kieda
Keyword(s):  
Endothelial Cells ◽  
Alternative Methods ◽  
Biological Processes ◽  
Animal Testing ◽  
Tissue Microenvironment ◽  
Vessel Permeability ◽  
Biological Phenomena ◽  
The Relationship ◽  
Different Tissues

Endothelial cells (ECs) lining the blood vessels are important players in many biological phenomena but are crucial in hypoxia-dependent diseases where their deregulation contributes to pathology. On the other hand, processes mediated by ECs, such as angiogenesis, vessel permeability, interactions with cells and factors circulating in the blood, maintain homeostasis of the organism. Understanding the diversity and heterogeneity of ECs in different tissues and during various biological processes is crucial in biomedical research to properly develop our knowledge on many diseases, including cancer. Here, we review the most important aspects related to ECs’ heterogeneity and list the available in vitro tools to study different angiogenesis-related pathologies. We focus on the relationship between functions of ECs and their organo-specificity but also point to how the microenvironment, mainly hypoxia, shapes their activity. We believe that taking into account the specific features of ECs that are relevant to the object of the study (organ or disease state), especially in a simplified in vitro setting, is important to truly depict the biology of endothelium and its consequences. This is possible in many instances with the use of proper in vitro tools as alternative methods to animal testing.

scholarly journals Mast Cells Interact with Endothelial Cells to Accelerate In Vitro Angiogenesis

2017 ◽  
Author(s):  
Devandir Antonio de Souza Junior ◽  
Vivian Marino Mazucato ◽  
Ana Carolina Santana ◽  
Constance Oliver ◽  
Maria Celia Jamur
Keyword(s):  
Endothelial Cells ◽  
Mast Cells ◽  
Intercellular Communication ◽  
Cell Types ◽  
Tissue Microenvironment ◽  
Complex Process ◽  
The Relationship ◽  
In Vitro Angiogenesis

Angiogenesis is a complex process that involves interactions between endothelial cells and various other cell types as well as the tissue microenvironment. Several previous studies have demonstrated that mast cells accumulate at angiogenic sites. In spite of the evidence suggesting a relationship between mast cells and angiogenesis, the association of mast cells and endothelial cells remains poorly understood. The present study aims to investigate the relationship between mast cells and endothelial cells during in vitro angiogenesis. When endothelial cells were co-cultured with mast cells, angiogenesis was stimulated. Furthermore, there was direct intercellular communication via gap junctions between the two cell types. In addition, the presence of mast cells stimulated endothelial cells to release angiogenic factors. Moreover, conditioned medium from the co-cultures also stimulated in vitro angiogenesis. The results from this investigation demonstrate that mast cells have both direct and indirect proangiogenic effects and provide new insights into the role of mast cells in angiogenesis.

scholarly journals Identification of urban particulate matter-induced disruption of human respiratory mucosa integrity using whole transcriptome analysis and organ-on-a chip

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Junhyoung Byun ◽  
Boa Song ◽  
Kyungwoo Lee ◽  
Byoungjae Kim ◽  
Hae Won Hwang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Particulate Matter ◽  
Epithelial Cells ◽  
Respiratory Mucosa ◽  
Nasal Epithelial Cells ◽  
Tissue Microenvironment ◽  
Human Nasal Epithelial Cells ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome

Abstract Background Exposure to air particulate matter (PM) is associated with various diseases in the human respiratory system. To date, most in vitro studies showing cellular responses to PM have been performed in cell culture using a single cell type. There are few studies considering how multicellular networks communicate in a tissue microenvironment when responding to the presence of PM. Here, an in vitro three-dimensional (3D) respiratory mucosa-on-a-chip, composed of human nasal epithelial cells, fibroblasts, and endothelial cells, is used to recapitulate and better understand the effects of urban particulate matter (UPM) on human respiratory mucosa. Results We hypothesized that the first cells to contact with UPM, the nasal epithelial cells, would respond similar to the tissue microenvironment, and the 3D respiratory mucosa model would be a suitable platform to capture these events. First, whole transcriptome analysis revealed that UPM induced gene expression alterations in inflammatory and adhesion-related genes in human nasal epithelial cells. Next, we developed an in vitro 3D respiratory mucosa model composed of human nasal epithelial cells, fibroblasts, and endothelial cells and demonstrated that the model is structurally and functionally compatible with the respiratory mucosa. Finally, we used our model to expose human nasal epithelial cells to UPM, which led to a disruption in the integrity of the respiratory mucosa by decreasing the expression of zonula occludens-1 in both the epithelium and endothelium, while also reducing vascular endothelial cadherin expression in the endothelium. Conclusions We demonstrate the potential of the 3D respiratory mucosa model as a valuable tool for the simultaneous evaluation of multicellular responses caused by external stimuli in the human respiratory mucosa. We believe that the evaluation strategy proposed in the study will move us toward a better understanding of the detailed molecular mechanisms associated with pathological changes in the human respiratory system.

Integrated Decision-tree Testing Strategies for Environmental Toxicity with Respect to the Requirements of the EU REACH Legislation

2008 ◽  
Vol 36 (1_suppl) ◽  
pp. 29-42 ◽  
Author(s):  
Christina Grindon ◽  
Robert Combes ◽  
Mark T.D. Cronin ◽  
David W. Roberts ◽  
John F. Garrod
Keyword(s):  
Risk Assessment ◽  
Decision Tree ◽  
Aquatic Toxicity ◽  
Toxicity Testing ◽  
Threshold Concentration ◽  
Alternative Methods ◽  
The European Union ◽  
Animal Testing ◽  
Testing Strategies

Liverpool John Moores University and FRAME recently conducted a research project sponsored by Defra on the status of alternatives to animal testing with regard to the European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for safety testing and risk assessment of chemicals. The project covered all the main toxicity endpoints associated with the REACH system. This paper focuses on the prospects for using alternative methods (both in vitro and in silico) for environmental (aquatic) toxicity testing. The manuscript reviews tests based on fish cells and cell lines, fish embryos, lower organisms, and the many expert systems and QSARs for aquatic toxicity testing. Ways in which reduction and refinement measures can be used are also discussed, including the Upper Threshold Concentration — Step Down (UTC) approach, which has recently been retrospectively validated by ECVAM and subsequently endorsed by the ECVAM Scientific Advisory Committee (ESAC). It is hoped that the application of this approach could reduce the number of fish used in acute toxicity studies by around 65–70%. Decision-tree style integrated testing strategies are also proposed for acute aquatic toxicity and chronic toxicity (including bioaccumulation), followed by a number of recommendations for the future facilitation of aquatic toxicity testing with respect to environmental risk assessment.

scholarly journals Association Between Gut Microbiota and Bone Health: Potential Mechanisms and Prospective

2017 ◽  
Vol 102 (10) ◽  
pp. 3635-3646 ◽  
Author(s):  
Yuan-Cheng Chen ◽  
Jonathan Greenbaum ◽  
Hui Shen ◽  
Hong-Wen Deng
Keyword(s):  
Gut Microbiota ◽  
Bone Metabolism ◽  
Bone Health ◽  
Association Studies ◽  
Evidence Synthesis ◽  
Critical Role ◽  
Mucosal Barrier ◽  
Biological Processes ◽  
The Relationship

Abstract Context It has been well established that the human gut microbiome plays a critical role in the regulation of important biological processes and the mechanisms underlying numerous complex diseases. Although researchers have only recently begun to study the relationship between the gut microbiota and bone metabolism, early efforts have provided increased evidence to suggest an important association. Evidence Acquisition In this study, we attempt to comprehensively summarize the relationship between the gut microbiota and bone metabolism by detailing the regulatory effects of the microbiome on various biological processes, including nutrient absorption and the intestinal mucosal barrier, immune system functionality, the gut–brain axis, and excretion of functional byproducts. In this review, we incorporate evidence from various types of studies, including observational, in vitro and in vivo animal experiments, as well as small efficacy clinic trails. Evidence Synthesis We review the various potential mechanisms of influence for the gut microbiota on the regulation of bone metabolism and discuss the importance of further examining the potential effects of the gut microbiota on the risk of osteoporosis in humans. Furthermore, we outline some useful tools/approaches for metagenomics research and present some prominent examples of metagenomics association studies in humans. Conclusion Current research efforts, although limited, clearly indicate that the gut microbiota may be implicated in bone metabolism, and therefore, further exploration of this relationship is a promising area of focus in bone health and osteoporosis research. Although most existing studies investigate this relationship using animal models, human studies are both needed and on the horizon.

scholarly journals Microfluidic measurement of cell motility in response to applied non-homogeneous DC electric fields

2016 ◽  
Vol 5 (2) ◽  
pp. 237-243
Author(s):  
Marisa Rio ◽  
Sharanya Bola ◽  
Richard H. W. Funk ◽  
Gerald Gerlach
Keyword(s):  
Electric Fields ◽  
Soft Lithography ◽  
Cellular Responses ◽  
Biological Processes ◽  
Biological Phenomena ◽  
Inverted Microscope ◽  
Directional Cell Migration ◽  
Insight Into ◽  
Dc Electric Fields

Abstract. Endogenous electric fields (EFs) play an important role in many biological processes. In order to gain an insight into these biological phenomena, externally applied electric fields are used to study cellular responses. In this work, we report the construction and fabrication of a direct current (DC)-electrically stimulated microfluidic biochip and its validation with murine photoreceptor-derived 661 W cells. The presented device has the particularity of offering a non-homogeneous EF environment that best resembles the endogenous electric fields in vitro. The fabrication process is relatively easy, namely by photolithography and soft lithography techniques and, furthermore, it enables live-cell imaging under an inverted microscope. First experimental results reveal cathodal directional cell migration upon applied DC EFs. In summary, the microfluidic biochip has proven biocompatibility and suitability for cellular electrotaxis experiments in non-homogeneous DC electric fields.

scholarly journals Distribution of microtubule organizing centers in migrating sheets of endothelial cells.

1981 ◽  
Vol 91 (2) ◽  
pp. 589-594 ◽  
Author(s):  
A I Gotlieb ◽  
L M May ◽  
L Subrahmanyan ◽  
V I Kalnins
Keyword(s):  
Endothelial Cells ◽  
Monolayer Culture ◽  
Cell Movement ◽  
Time Lapse ◽  
Microtubule Organizing Center ◽  
Organizing Center ◽  
Direction Of Movement ◽  
The Relationship ◽  
Wounded Area

This study was designed to investigate the relationship between the position of the microtubule organizing center (MTOC) and the direction of migration of a sheet of endothelial cells (EC). Using immunofluorescence and phase microscopy the MTOC's of migrating EC were visualized as the cells moved into an in vitro experimental wound produced by mechanical denudation of part of a confluent monolayer culture. Although the MTOC's in nonmigrating EC were randomly positioned in relation to the nucleus, in migrating cells the position of the MTOC's changed so that 80% of the cells had the MTOC positioned in front of the nucleus toward the direction of movement of the endothelial sheet. This repositioning of the MTOC occurred within the first 4 h after wounding and was associated with the beginning of migration of EC's into the wounded area as seen by time-lapse cinemicrophotography. These studies focus attention on the MTOC as a cytoskeletal structure that may play a role in determining the direction of cell movement.

Permeability of neutral vs. anionic dextrans in cultured brain microvascular endothelium

1990 ◽  
Vol 259 (1) ◽  
pp. H162-H166 ◽  
Author(s):  
G. Sahagun ◽  
S. A. Moore ◽  
M. N. Hart
Keyword(s):  
Endothelial Cells ◽  
Endothelial Permeability ◽  
Cell Permeability ◽  
Microvascular Endothelium ◽  
Endothelial Surface ◽  
Luminal Side ◽  
Brain Microvessel ◽  
Relationship Of ◽  
The Relationship

The luminal surface of vascular endothelium contains glycocalyx residues that establish an overall negative charge. Recent evidence has suggested that local endothelial surface charge properties may account for the permeability properties of various macromolecules. It has also been suggested that altered membrane charge on the luminal side may play a role in thrombogenesis and atherogenesis. The relationship of macromolecule charge to endothelial cell permeability was examined in vitro using mouse brain microvessel endothelial cells grown to confluence on a nitrocellulose filter separating a double-chamber system. Endothelial permeability to 4K and 10K fluorescein-labeled neutral dextrans was compared with the permeability to 4K and 10K fluorescein-labeled anionic dextrans (sulfated). After 1 h, there was significantly greater permeability of neutral fluorescein-labeled dextran than of anionic fluorescein-labeled dextran in each particle size. In addition, there was significantly greater permeability of 4K than 10K fluorescein-labeled dextrans of either charge. The findings indicate that charge in addition to size plays an important role in the movement of macromolecules across cultured microvascular endothelial cells.

scholarly journals Evaluation of Strategies Aimed at Improving Liver Progenitor Cell Rolling and Subsequent Adhesion to the Endothelium

2020 ◽  
Vol 29 ◽  
pp. 096368972091270
Author(s):  
Pierre Edouard Dollet ◽  
Mei Ju Hsu ◽  
Jérôme Ambroise ◽  
Milena Rozzi ◽  
Joachim Ravau ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Alternative Methods ◽  
Sialyl Lewis X ◽  
Thermosensitive Polymer ◽  
Lewis X ◽  
Promising Alternative ◽  
Sialyl Lewis ◽  
Selectin Ligand

Adult-derived human liver stem/progenitor cells (ADHLSCs) are a promising alternative to orthotopic liver transplantation in the treatment of inborn errors of metabolism. However, as is the case with many mesenchymal stromal cells, ADHLSCs have shown a low level of engraftment, which could be explained by the fact that they lack expression of selectin ligand and LFA-1 and only slightly express VLA- 4, molecules that have been shown to be involved in cell adhesion to the endothelium. In this paper, we have investigated strategies to increase their rolling and adhesion during the homing process by (1) adding a selectin ligand (Sialyl Lewis X) to their surface using biotinyl- N-hydroxy-succinimide–streptavidin bridges, and (2) protecting the adhesion proteins from trypsinization-induced damage using a thermosensitive polymer for cell culture and a nonenzymatic cell dissociation solution (CDS) for harvest. Despite increasing adhesion of ADHLSCs to E-selectin during an adhesion test in vitro performed under shear stress, the addition of Sialyl Lewis X did not increase adhesion to endothelial cells under the same conditions. Cultivating cells on a thermosensitive polymer and harvesting them with CDS increased their adhesion to endothelial cells under noninflammatory conditions, compared to the use of trypsin. However, we were not able to demonstrate any improvement in cell adhesion to the endothelium following culture on polymer and harvest with CDS, suggesting that alternative methods of improving engraftment still need to be evaluated.

scholarly journals Adverse effects of organophosphorus pesticides on the liver: a brief summary of four decades of research

2017 ◽  
Vol 68 (4) ◽  
pp. 261-275 ◽  
Author(s):  
Somayyeh Karami-Mohajeri ◽  
Ahmad Ahmadipour ◽  
Hamid-Reza Rahimi ◽  
Mohammad Abdollahi
Keyword(s):  
Oxidative Stress ◽  
Organophosphorus Pesticides ◽  
Review Article ◽  
Biological Processes ◽  
Antioxidant Defence ◽  
Antioxidant Defence System ◽  
The Relationship ◽  
Harmful Effects

Abstract Organophosphorus pesticides (OPs) are widely used volatile pesticides that have harmful effects on the liver in acute and chronic exposures. This review article summarises and discusses a wide collection of studies published over the last 40 years reporting on the effects of OPs on the liver, in an attempt to propose general mechanisms of OP hepatotoxicity and possible treatment. Several key biological processes have been reported as involved in OP-induced hepatotoxicity such as disturbances in the antioxidant defence system, oxidative stress, apoptosis, and mitochondrial and microsomal metabolism. Most studies show that antioxidants can attenuate oxidative stress and the consequent changes in liver function. However, few studies have examined the relationship between OP structures and the severity and mechanism of their action. We hope that future in vitro, in vivo, and clinical trials will answer the remaining questions about the mechanisms of OP hepatotoxicity and its management.

Local Irritation/Corrosion Testing Strategies: Development of a Decision Support System for the Introduction of Alternative Methods

2000 ◽  
Vol 28 (1) ◽  
pp. 29-40 ◽  
Author(s):  
Stephan Zinke ◽  
Ingrid Gerner ◽  
Gabriele Graetschel ◽  
Eva Schlede
Keyword(s):  
Decision Support ◽  
Decision Support System ◽  
Support System ◽  
Chemical Properties ◽  
Alternative Methods ◽  
In Vitro Tests ◽  
The European Union ◽  
Animal Testing ◽  
Property A

The notification procedure for new chemicals of the European Union (EU) requires protocols on physicochemical and toxicological tests for the evaluation of physico-chemical properties and probable toxic effects of each notified substance. In order to reduce the amount of animal testing, alternative methods should be introduced into toxicity testing. Therefore, we have developed a rule-based decision support system (DSS) for the prediction of the local corrosive/irritant properties of new chemicals. To this end, data on more than 1000 substances were examined, which resulted in approximtely 180 “exception-rules” of the kind IF (physicochemical property) A THEN not (toxic) Effect B. In addition, the structural formulae of the chemicals were analysed, which resulted in approximately 160 “structure-rules” of the kind IF Substructure A THEN Effect B. The DSS can predict (based on theoretical structure-activity relationships) whether a chemical produces: a) corrosive effects (i.e. no testing is necessary; b) might have corrosive effects (i.e. no animal testing, in vitro tests are suitable); and c) will produce no effects or only marginal effects (i.e. animal tests are necessary based on current EU legislation for hazard assessment purposes). In addition, the DSS provides reliable data for legal classification and labelling based on a specific result.

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