scholarly journals Three-Dimensional Cell Culture Models to Study Respiratory Virus Infections Including COVID-19

Biomimetics ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. 3
Author(s):  
Aya Harb ◽  
Mohammad Fakhreddine ◽  
Hassan Zaraket ◽  
Fatima A. Saleh
Keyword(s):  
Viral Infections ◽  
Three Dimensional ◽  
3D Culture ◽  
3D Models ◽  
Respiratory Viruses ◽  
Model Systems ◽  
Virus Infections ◽  
Culture Models ◽  
Syncytial Virus

Respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are among the most common illnesses and a leading cause of morbidity and mortality worldwide. Due to the severe effects on health, the need of new tools to study the pathogenesis of respiratory viruses as well as to test for new antiviral drugs and vaccines is urgent. In vitro culture model systems, such as three-dimensional (3D) cultures, are emerging as a desirable approach to understand the virus host interactions and to identify novel therapeutic agents. In the first part of the article, we address the various scaffold-free and scaffold-based 3D culture models such as hydrogels, bioreactors, spheroids and 3D bioprinting as well as present their properties and advantages over conventional 2D methods. Then, we review the 3D models that have been used to study the most common respiratory viruses including influenza, parainfluenza, respiratory syncytial virus (RSV) and coronaviruses. Herein, we also explain how 3D models have been applied to understand the novel SARS-CoV-2 infectivity and to develop potential therapies.

scholarly journals Beyond 3D culture models of cancer

2015 ◽  
Vol 7 (283) ◽  
pp. 283ps9-283ps9 ◽  
Author(s):  
Kandice Tanner ◽  
Michael M. Gottesman
Keyword(s):  
In Vitro Culture ◽  
Three Dimensional ◽  
3D Culture ◽  
Drug Efficacy ◽  
Spatiotemporal Evolution ◽  
Culture Models ◽  
Dynamic Interplay

The mechanisms underlying the spatiotemporal evolution of tumor ecosystems present a challenge in evaluating drug efficacy. In this Perspective, we address the use of three-dimensional in vitro culture models to delineate the dynamic interplay between the tumor and the host microenvironment in an effort to attain realistic platforms for assessing pharmaceutical efficacy in patients.

scholarly journals In vitro model systems to study androgen receptor signaling in prostate cancer

2013 ◽  
Vol 20 (2) ◽  
pp. R49-R64 ◽  
Author(s):  
Natalie Sampson ◽  
Hannes Neuwirt ◽  
Martin Puhr ◽  
Helmut Klocker ◽  
Iris E Eder
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cellular Response ◽  
Three Dimensional ◽  
Model Systems ◽  
Transfer Of Knowledge ◽  
Prostate Epithelial Cells ◽  
Technological Advances ◽  
Culture Models

Prostate cancer (PCa) is one of the most common causes of male cancer-related death in Western nations. The cellular response to androgens is mediated via the androgen receptor (AR), a ligand-inducible transcription factor whose dysregulation plays a key role during PCa development and progression following androgen deprivation therapy, the current mainstay systemic treatment for advanced PCa. Thus, a better understanding of AR signaling and new strategies to abrogate AR activity are essential for improved therapeutic intervention. Consequently, a large number of experimental cell culture models have been established to facilitate in vitro investigations into the role of AR signaling in PCa development and progression. These different model systems mimic distinct stages of this heterogeneous disease and exhibit differences with respect to AR expression/status and androgen responsiveness. Technological advances have facilitated the development of in vitro systems that more closely reflect the physiological setting, for example via the use of three-dimensional coculture to study the interaction of prostate epithelial cells with the stroma, endothelium, immune system and tissue matrix environment. This review provides an overview of the most commonly used in vitro cell models currently available to study AR signaling with particular focus on their use in addressing key questions relating to the development and progression of PCa. It is hoped that the continued development of in vitro models will provide more biologically relevant platforms for mechanistic studies, drug discovery and design ensuring a more rapid transfer of knowledge from the laboratory to the clinic.

scholarly journals Modified cyclodextrins as broad-spectrum antivirals

2020 ◽  
Vol 6 (5) ◽  
pp. eaax9318 ◽  
Author(s):  
Samuel T. Jones ◽  
Valeria Cagno ◽  
Matej Janeček ◽  
Daniel Ortiz ◽  
Natalia Gasilova ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Viral Infections ◽  
Ex Vivo ◽  
Vaginal Tissue ◽  
Modified Cyclodextrins ◽  
Culture Models ◽  
Heparan Sulfates ◽  
Syncytial Virus ◽  
Simplex Virus

Viral infections kill millions of people and new antivirals are needed. Nontoxic drugs that irreversibly inhibit viruses (virucidal) are postulated to be ideal. Unfortunately, all virucidal molecules described to date are cytotoxic. We recently developed nontoxic, broad-spectrum virucidal gold nanoparticles. Here, we develop further the concept and describe cyclodextrins, modified with mercaptoundecane sulfonic acids, to mimic heparan sulfates and to provide the key nontoxic virucidal action. We show that the resulting macromolecules are broad-spectrum, biocompatible, and virucidal at micromolar concentrations in vitro against many viruses [including herpes simplex virus (HSV), respiratory syncytial virus (RSV), dengue virus, and Zika virus]. They are effective ex vivo against both laboratory and clinical strains of RSV and HSV-2 in respiratory and vaginal tissue culture models, respectively. Additionally, they are effective when administrated in mice before intravaginal HSV-2 inoculation. Lastly, they pass a mutation resistance test that the currently available anti-HSV drug (acyclovir) fails.

scholarly journals 3D cell culture technology – a new insight into in vitro research – a review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Justyna Sośniak ◽  
Jolanta Opiela
Keyword(s):  
Three Dimensional ◽  
3D Culture ◽  
3D Cell Culture ◽  
2D Systems ◽  
Multicellular Spheroids ◽  
Advantages And Disadvantages ◽  
3D Cell Cultures ◽  
Culture Models ◽  
Culture Technology

Abstract Most in vitro cell-based research is based on two-dimensional (2D) systems where growth and development take place on a flat surface, which does not reflect the natural environment of the cells. The imperfection and limitations of culture in 2D systems eventually led to the creation of three-dimensional (3D) culture models that more closely reproduce the actual conditions of physiological cell growth. Since the inception of 3D culture technology, many culture models have been developed, such as technologies of multicellular spheroids, organoids, and organs on chips in the technology of scaffolding, hydrogels, bio-printing and liquid media. In this review we will focus on the advantages and disadvantages of the 2D vs. 3D cell cultures technologies. We will also try to sum up available 3D cultures systems and materials for building 3D scaffolds.

Comparison of two-dimensional (2D)- and three-dimensional (3D)-culture models as drug testing platforms in GIST: experience with axitinib in vitro

2017 ◽  
Vol 72 ◽  
pp. S155
Author(s):  
V. Martínez-Marín ◽  
A. Redondo ◽  
V. Heredia ◽  
L. Guerra ◽  
M. Miguel-Martín ◽  
...  
Keyword(s):  
Drug Testing ◽  
Three Dimensional ◽  
3D Culture ◽  
Two Dimensional ◽  
Culture Models

scholarly journals Crosstalk between invadopodia and the extracellular matrix

2020 ◽  
Author(s):  
Shinji Iizuka ◽  
Ronald P. Leon ◽  
Kyle P. Gribbin ◽  
Ying Zhang ◽  
Jose Navarro ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Complex Structure ◽  
Three Dimensional ◽  
3D Culture ◽  
Model Systems ◽  
Type I ◽  
Extracellular Matrix Components

ABSTRACTThe scaffold protein Tks5α is required for invadopodia-mediated cancer invasion both in vitro and in vivo. We have previously also revealed a role for Tks5 in tumor cell growth using three-dimensional (3D) culture model systems and mouse transplantation experiments. Here we use both 3D and high-density fibrillar collagen (HDFC) culture to demonstrate that native type I collagen, but not a form lacking the telopeptides, stimulated Tks5-dependent growth, which was dependent on the DDR collagen receptors. We used microenvironmental microarray (MEMA) technology to determine that laminin, collagen I, fibronectin and tropoelastin also stimulated invadopodia formation. A Tks5α-specific monoclonal antibody revealed its expression both on microtubules and at invadopodia. High- and super-resolution microscopy of cells in and on collagen was then used to place Tks5α at the base of invadopodia, separated from much of the actin and cortactin, but coincident with both matrix metalloprotease and cathepsin proteolytic activity. Inhibition of the Src family kinases, cathepsins or metalloproteases all reduced invadopodia length but each had distinct effects on Tks5α localization. These studies highlight the crosstalk between invadopodia and extracellular matrix components, and reveal the invadopodium to be a spatially complex structure.

scholarly journals Multiparametric investigation of non functionalized-AGuIX nanoparticles in 3D human airway epithelium models demonstrates preferential targeting of tumor cells

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Lucie Sancey ◽  
Odile Sabido ◽  
Zhiguo He ◽  
Fabien Rossetti ◽  
Alain Guignandon ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Therapeutic Potential ◽  
3D Culture ◽  
Small Animal ◽  
3D Models ◽  
Tumor Bearing ◽  
Human Airway Epithelium ◽  
3D Cell Cultures ◽  
Culture Models

Abstract Liquid deposit mimicking surface aerosolization in the airway is a promising strategy for targeting bronchopulmonary tumors with reduced doses of nanoparticle (NPs). In mimicking and studying such delivery approaches, the use of human in vitro 3D culture models can bridge the gap between 2D cell culture and small animal investigations. Here, we exposed airway epithelia to liquid-apical gadolinium-based AGuIX® NPs in order to determine their safety profile. We used a multiparametric methodology to investigate the NP’s distribution over time in both healthy and tumor-bearing 3D models. AGuIX® NPs were able to target tumor cells in the absence of specific surface functionalization, without evidence of toxicity. Finally, we validated the therapeutic potential of this hybrid theranostic AGuIX® NPs upon radiation exposure in this model. In conclusion, 3D cell cultures can efficiently mimic the normal and tumor-bearing airway epitheliums, providing an ethical and accessible model for the investigation of nebulized NPs.

scholarly journals 3D Models as an Adjunct for Models in Studying Alzheimer’s Disease

2021 ◽  
Author(s):  
Ahmed Yaqinuddin ◽  
Muhammad Faisal Ikram ◽  
Ayesha Rahman Ambia ◽  
Raghad Alaujan ◽  
Junaid Kashir
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Three Dimensional ◽  
3D Culture ◽  
Amyloid Β ◽  
3D Models ◽  
Culture Models ◽  
Neurological Processes

AbstractAlzheimer’s disease (AD) is one of the most common causes of dementia. Disease progression is marked by cognitive decline and memory impairment due to neurodegenerative processes in the brain stemming from amyloid-β (Aβ) deposition and formation of neurofibrillary tangles. Pathogenesis in AD is dependent on two main neurological processes: formation of intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein and deposition of extracellular senile Aβ peptides. Given the nature of the disease, the pathology and progression of AD in vivo in humans have been difficult to study in vivo. To this degree, models can help to study the disease pathogenesis, biochemistry, immunological functions, genetics, and potential pharmacotherapy. While animal and two-dimensional (2D) cell culture models have facilitated significant progress in studying the disease, more recent application of novel three-dimensional (3D) culture models has exhibited several advantages. Herein, we describe a brief background of AD, and how current animal, 2D, and 3D models facilitate the study of this disease and associated therapeutics.

scholarly journals Are Respiratory Viruses Involved in Preseasonal Symptoms or Severity in Japanese Cedar Pollinosis?

2016 ◽  
Vol 7 (2) ◽  
pp. ar.2016.7.0157 ◽  
Author(s):  
Hirokuni Otsuka ◽  
Hiroyuki Tsukagoshi ◽  
Hirokazu Kimura ◽  
Ikuo Takanashi ◽  
Kimihiro Okubo
Keyword(s):  
Respiratory Virus ◽  
Viral Infections ◽  
Japanese Cedar ◽  
Respiratory Viruses ◽  
Virus Infections ◽  
Significant Difference ◽  
Syncytial Virus ◽  
Japanese Cedar Pollinosis ◽  
Respiratory Virus Infections ◽  
The Relationship

Background Respiratory virus infections are involved in asthma exacerbations. However, there are no reports of the relationship between respiratory virus infections and Japanese cedar pollinosis. Objective We studied the relationship between respiratory viral infection and the appearance of preseasonal symptoms and the severity of seasonal symptoms in Japanese cedar pollinosis. Methods In 36 patients with asthma and with no symptoms (PreAsyP) and 54 patients with asthma and with symptoms (PreSyP) before the cedar pollen shedding commenced (preseason), and 37 patients with mild-to-moderate severity (InMild/Mod) and 45 patients with severe to extreme severity (InSev/Ext) after cedar shedding commenced (in season), the occurrence of respiratory viruses and nasal smear cytology were examined. Results In total, seven infections with respiratory viruses were detected among the subjects. Human rhinovirus (HRV) C infection was detected in one subject in each of the PreAsyP and PreSyP groups, and one HRVA infection occurred in the InMild/Mod group. In the InSev/Ext group, one HRVA, one HRVC, one respiratory syncytial virus, and one human metapneumovirus were detected. There was no significant difference in the rate of detection of viral infections between the PreAsyP and the PreSyP groups (p = 0.077), and between the InMild/Mod group and the InSev/Ext group (p = 0.24, Wilcoxon rank sum test). When cells types in nasal smears were identified and their abundance examined, the rate of neutrophilia in the subjects in the PreSyP group was 54%, which was statistically higher (p < 0.01) than the subjects in the PreAsyP group (25%). Interestingly, in the subjects in the InSev/Ext group, the proportion of eosinophils (40%) was larger (p < 0.05) than in the subjects in the InMild/Mod group (19%). Conclusion These results provided no evidence that respiratory virus infections contributed to preseasonal symptoms and severity in season of Japanese cedar pollinosis. Nasal neutrophilia was related to preseasonal symptoms, whereas nasal eosinophilia was related to severity of symptoms during the pollen season.

scholarly journals Unforeseen decreases in dissolved oxygen levels affect tube formation kinetics in collagen gels

2011 ◽  
Vol 301 (2) ◽  
pp. C431-C440 ◽  
Author(s):  
Hasan Erbil Abaci ◽  
Rachel Truitt ◽  
Scott Tan ◽  
Sharon Gerecht
Keyword(s):  
Dissolved Oxygen ◽  
Umbilical Vein ◽  
Three Dimensional ◽  
3D Culture ◽  
Tube Formation ◽  
Atmospheric Conditions ◽  
Collagen Gels ◽  
Culture Models ◽  
Umbilical Vein Endothelial Cells

The availability of oxygen (O2) is a critical parameter affecting vascular tube formation. In this study, we hypothesize that dissolved oxygen (DO) levels in collagen gels change during the three-dimensional (3D) culture of human umbilical vein endothelial cells (HUVECs) in atmospheric conditions and that such changes affect the kinetics of tube formation through the production of reactive oxygen species (ROS). We demonstrate a decrease in O2tension during 3D cultures of HUVECs. Noninvasive measurements of DO levels during culture under atmospheric conditions revealed a profound decrease that reached as low as 2% O2at the end of 24 h. After media replacement, DO levels rose rapidly and equilibrated at ∼15% O2, creating a reoxygenated environment. To accurately estimate DO gradients in 3D collagen gels, we developed a 3D mathematical model and determined the Michaelis-Menten parameters, Vmaxand Km, of HUVECs in collagen gels. We detected an increase in ROS levels throughout the culture period. Using diphenyliodonium to inhibit ROS production resulted in the complete inhibition of tube formation. Interference RNA studies further showed that hypoxia-inducible factors (HIFs)-1α and -2α are not involved in the formation of 3D tubes in collagen gels. We conclude that ROS affect the tubulogenesis process through HIFα-independent pathways, where the levels of ROS are influenced by the uncontrolled variations in DO levels. This study is the first demonstration of the critical and unexpected role of O2during 3D in vitro culture models of tubulogenesis in atmospheric conditions.

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