scholarly journals Clinically relevant cell culture models and their significance in isolation, pathogenesis, vaccine development, repurposing and screening of new drugs for SARS-CoV-2: a systematic review

2021 ◽  
Vol 70 ◽  
pp. 101497
Author(s):  
Subodh Kumar ◽  
Phulen Sarma ◽  
Hardeep Kaur ◽  
Manisha Prajapat ◽  
Anusuya Bhattacharyya ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cell Culture ◽  
Vaccine Development ◽  
New Drugs ◽  
Culture Models ◽  
Cell Culture Models

scholarly journals Tissue Engineering of Oral Mucosa and Salivary Gland: Disease Modeling and Clinical Applications

Micromachines ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1066
Author(s):  
Akram Abdo Almansoori ◽  
Bongju Kim ◽  
Jong-Ho Lee ◽  
Simon D. Tran
Keyword(s):  
Cell Culture ◽  
Salivary Gland ◽  
Oral Mucosa ◽  
Disease Modeling ◽  
Clinical Applications ◽  
New Drugs ◽  
Human Organ ◽  
Culture Models ◽  
Cell Culture Models

Oral mucosa and salivary gland are composed of complex and dynamic networks of extracellular matrix, multiple cell types, vasculature, and various biochemical agents. Two-dimensional (2D) cell culture is commonly used in testing new drugs and experimental therapies. However, 2D cell culture cannot fully replicate the architecture, physiological, and pathological microenvironment of living human oral mucosa and salivary glands. Recent microengineering techniques offer state of the science cell culture models that can recapitulate human organ structures and functions. This narrative review describes emerging in vitro models of oral and salivary gland tissue such as 3D cell culture models, spheroid and organoid models, tissue-on-a-chip, and functional decellularized scaffolds. Clinical applications of these models are also discussed in this review.

scholarly journals 3D Tissue Models as an Effective Tool for Studying Viruses and Vaccine Development

2021 ◽  
Vol 8 ◽  
Author(s):  
Nathan Lawko ◽  
Charlie Plaskasovitis ◽  
Carling Stokes ◽  
Laila Abelseth ◽  
Ian Fraser ◽  
...  
Keyword(s):  
Cell Culture ◽  
Drug Discovery ◽  
Vaccine Development ◽  
Rapid Development ◽  
3D Cell Culture ◽  
Host Cells ◽  
Culture Models ◽  
Cell Culture Models ◽  
Cell Cell

The recent SARS-CoV-2 outbreak has researchers working tirelessly to understand the virus' pathogenesis and develop an effective vaccine. The urgent need for rapid development and deployment of such a vaccine has illustrated the limitations of current practices, and it has highlighted the need for alternative models for early screening of such technologies. Traditional 2D cell culture does not accurately capture the effects of a physiologically relevant environment as they fail to promote appropriate cell-cell and cell-environment interactions. This inability to capture the intricacies of the in vivo microenvironment prevents 2D cell cultures from demonstrating the necessary properties of native tissues required for the standard infection mechanisms of the virus, thus contributing the high failure rate of drug discovery and vaccine development. 3D cell culture models can bridge the gap between conventional cell culture and in vivo models. Methods such as 3D bioprinting, spheroids, organoids, organ-on-chip platform, and rotating wall vessel bioreactors offer ways to produce physiologically relevant models by mimicking in vivo microarchitecture, chemical gradients, cell–cell interactions and cell–environment interactions. The field of viral biology currently uses 3D cell culture models to understand the interactions between viruses and host cells, which is crucial knowledge for vaccine development. In this review, we discuss how 3D cell culture models have been used to investigate disease pathologies for coronaviruses and other viruses such as Zika Virus, Hepatitis, and Influenza, and how they may apply to drug discovery and vaccine development.

scholarly journals Analysis of interleukin-1 receptor associated kinase-3 (IRAK3) function in modulating expression of inflammatory markers in cell culture models: A systematic review and meta-analysis

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244570
Author(s):  
Trang Hong Nguyen ◽  
Ilona Turek ◽  
Terri Meehan-Andrews ◽  
Anita Zacharias ◽  
Helen Irving
Keyword(s):  
Systematic Review ◽  
Cell Culture ◽  
Cell Lines ◽  
Outcome Measures ◽  
Inflammatory Markers ◽  
Primary Cells ◽  
Tnf Α ◽  
Culture Models ◽  
Meta Analyses ◽  
Cell Culture Models

Background IRAK3 is a critical modulator of inflammation in innate immunity. IRAK3 is associated with many inflammatory diseases, including sepsis, and is required in endotoxin tolerance to maintain homeostasis of inflammation. The impact of IRAK3 on inflammatory markers such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cell culture models remains controversial. Objective To analyse temporal effects of IRAK3 on inflammatory markers after one- or two-challenge interventions in cell culture models. Methods A systematic search was performed to identify in vitro cell studies reporting outcome measures of expression of IRAK3 and inflammatory markers. Meta-analyses were performed where sufficient data were available. Comparisons of outcome measures were performed between different cell lines and human and mouse primary cells. Results The literature search identified 7766 studies for screening. After screening titles, abstracts and full-texts, a total of 89 studies were included in the systematic review. Conclusions The review identifies significant effects of IRAK3 on decreasing NF-κB DNA binding activity in cell lines, TNF-α protein level at intermediate time intervals (4h–15h) in cell lines or at long term intervals (16h–48h) in mouse primary cells following one-challenge. The patterns of TNF-α protein expression in human cell lines and human primary cells in response to one-challenge are more similar than in mouse primary cells. Meta-analyses confirm a negative correlation between IRAK3 and inflammatory cytokine (IL-6 and TNF-α) expression after two-challenges.

scholarly journals Factors to consider when interrogating 3D culture models with plate readers or automated microscopes

2021 ◽  
Author(s):  
Terry Riss ◽  
O. Joseph Trask
Keyword(s):  
Cell Culture ◽  
Three Dimensional ◽  
3D Culture ◽  
Fluorescent Imaging ◽  
Culture Models ◽  
Assay Methods ◽  
Diffusion Rates ◽  
Cell Culture Models ◽  
Dimensional Cell ◽  
Cells Cultured

AbstractAlong with the increased use of more physiologically relevant three-dimensional cell culture models comes the responsibility of researchers to validate new assay methods that measure events in structures that are physically larger and more complex compared to monolayers of cells. It should not be assumed that assays designed using monolayers of cells will work for cells cultured as larger three-dimensional masses. The size and barriers for penetration of molecules through the layers of cells result in a different microenvironment for the cells in the outer layer compared to the center of three-dimensional structures. Diffusion rates for nutrients and oxygen may limit metabolic activity which is often measured as a marker for cell viability. For assays that lyse cells, the penetration of reagents to achieve uniform cell lysis must be considered. For live cell fluorescent imaging assays, the diffusion of fluorescent probes and penetration of photons of light for probe excitation and fluorescent emission must be considered. This review will provide an overview of factors to consider when implementing assays to interrogate three dimensional cell culture models.

scholarly journals Turnover of the Active Fraction of IRS1 Involves Raptor-mTOR- and S6K1-Dependent Serine Phosphorylation in Cell Culture Models of Tuberous Sclerosis

2006 ◽  
Vol 26 (17) ◽  
pp. 6425-6434 ◽  
Author(s):  
O. Jameel Shah ◽  
Tony Hunter
Keyword(s):  
Cell Culture ◽  
Tuberous Sclerosis ◽  
High Speed ◽  
Serine Phosphorylation ◽  
Feedback Signal ◽  
Insulin Receptor Substrates ◽  
Igf I ◽  
Culture Models ◽  
Cell Culture Models

ABSTRACT The TSC1-TSC2/Rheb/Raptor-mTOR/S6K1 cell growth cassette has recently been shown to regulate cell autonomous insulin and insulin-like growth factor I (IGF-I) sensitivity by transducing a negative feedback signal that targets insulin receptor substrates 1 and 2 (IRS1 and -2). Using two cell culture models of the familial hamartoma syndrome, tuberous sclerosis, we show here that Raptor-mTOR and S6K1 are required for phosphorylation of IRS1 at a subset of serine residues frequently associated with insulin resistance, including S307, S312, S527, S616, and S636 (of human IRS1). Using loss- and gain-of-function S6K1 constructs, we demonstrate a requirement for the catalytic activity of S6K1 in both direct and indirect regulation of IRS1 serine phosphorylation. S6K1 phosphorylates IRS1 in vitro on multiple residues showing strong preference for RXRXXS/T over S/T,P sites. IRS1 is preferentially depleted from the high-speed pellet fraction in TSC1/2-deficient mouse embryo fibroblasts or in HEK293/293T cells overexpressing Rheb. These studies suggest that, through serine phosphorylation, Raptor-mTOR and S6K1 cell autonomously promote the depletion of IRS1 from specific intracellular pools in pathological states of insulin and IGF-I resistance and thus potentially in lesions associated with tuberous sclerosis.

Cell culture models of the ocular barriers

2005 ◽  
Vol 60 (2) ◽  
pp. 207-225 ◽  
Author(s):  
Margit Hornof ◽  
Elisa Toropainen ◽  
Arto Urtti
Keyword(s):  
Cell Culture ◽  
Culture Models ◽  
Cell Culture Models

Abstract 15951: Palmitate, Not Oleate, is the Preferred Fatty Acid for Cardiac Triacylglycerol Synthesis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Stephen C Kolwicz ◽  
Rong Tian
Keyword(s):  
Cell Culture ◽  
13C Nmr Spectroscopy ◽  
Culture Studies ◽  
Triacylglycerol Synthesis ◽  
Culture Models ◽  
Contracting Heart ◽  
And Control ◽  
The Relationship ◽  
Cell Culture Models ◽  
Insight Into

Introduction: Previous studies using cell culture models identified cyto-toxic effects of palmitate and that supplementation with oleate was protective by redirecting palmitate into triacylglycerol (TAG) stores. However, other cull culture studies reported that diacylglycerol transferase 1 (DGAT1), the last enzyme in TAG synthesis, demonstrated a preference for oleate. At present, it is not clear whether the supply of exogenous fatty acids (FA) to the heart is differentially allocated into the endogenous TAG pool. Therefore, the purpose of the present study is to examine the influence of palmitate and/or oleate on cardiac TAG incorporation. METHODS/RESULTS: Hearts were isolated from DGAT1-transgenic (DGAT) and control littermates (CON) and perfused in Langendorff mode with a mixed substrate buffer consisting of glucose, lactate, insulin, and FAs. The FA supply was varied with 0.2mM of both labeled (13C) and unlabeled (12C) FAs in 4 different experiments: 1) 13C/12C palmitate; 2) 13C/12C oleate; 3) 13C palmitate/12C oleate; 4) 13C oleate/12C palmitate. The incorporation of 13C palmitate or 13C oleate into the TAG pool was monitored by 13C NMR spectroscopy. In CON hearts (n=3), the incorporation of palmitate was ~65% higher than oleate when the perfusate contained a homogenous supply of FA. This was also observed in DGAT hearts (n=4) although the incorporation of both palmitate and oleate was ~75% higher compared to CON (P <0.05). In the presence of oleate, palmitate incorporation decreased 25-30% in both CON and DGAT hearts. In contrast, oleate incorporation was diminished by ~50% and ~100% in CON and DGAT hearts, respectively, in the presence of palmitate. CONCLUSIONS: These data suggest that when palmitate and oleate are provided in equal concentrations, palmitate is more readily utilized in the synthesis of endogenous TAG stores in the heart. Furthermore, although overexpression of DGAT increases both oleate and palmitate incorporation, the DGAT1 enzyme demonstrates a preference for palmitate. These findings provide insight into the relationship between exogenous FA supply and endogenous TAG dynamics in the contracting heart.

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