scholarly journals Human immunocompetent choroid-on-chip: a novel tool for studying ocular effects of biological drugs

2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Madalena Cipriano ◽  
Katharina Schlünder ◽  
Christopher Probst ◽  
Kirstin Linke ◽  
Martin Weiss ◽  
...  
Keyword(s):  
Immune Cell ◽  
Complex Model ◽  
Model Systems ◽  
Biological Drugs ◽  
Mechanisms Of Toxicity ◽  
Vitro Model ◽  
On Chip ◽  
Peripheral Immune Cells

AbstractDisorders of the eye leading to visual impairment are a major issue that affects millions of people. On the other side ocular toxicities were described for e.g. molecularly targeted therapies in oncology and may hamper their development. Current ocular model systems feature a number of limitations affecting human-relevance and availability. To find new options for pharmacological treatment and assess mechanisms of toxicity, hence, novel complex model systems that are human-relevant and readily available are urgently required. Here, we report the development of a human immunocompetent Choroid-on-Chip (CoC), a human cell-based in vitro model of the choroid layer of the eye integrating melanocytes and microvascular endothelial cells, covered by a layer of retinal pigmented epithelial cells. Immunocompetence is achieved by perfusion of peripheral immune cells. We demonstrate controlled immune cell recruitment into the stromal compartments through a vascular monolayer and in vivo-like cytokine release profiles. To investigate applicability for both efficacy testing of immunosuppressive compounds as well as safety profiling of immunoactivating antibodies, we exposed the CoCs to cyclosporine and tested CD3 bispecific antibodies.

scholarly journals Human immunocompetent Choroid-on-Chip: a novel tool for studying ocular effects of biological drugs

2021 ◽  
Author(s):  
Madalena Cipriano ◽  
Katharina Schluender ◽  
Christopher Probst ◽  
Kirstin Linke ◽  
Martin Weiss ◽  
...  
Keyword(s):  
Immune Cell ◽  
Complex Model ◽  
Model Systems ◽  
Biological Drugs ◽  
Mechanisms Of Toxicity ◽  
Vitro Model ◽  
On Chip ◽  
Peripheral Immune Cells

Disorders of the eye leading to visual impairment are a major issue that affects millions of people. On the other side ocular toxicities were described for e.g. molecularly targeted therapies in oncology and may hamper their development. Current ocular model systems feature a number of limitations affecting human-relevance and availability. To find new options for pharmacological treatment and assess mechanisms of toxicity, hence, novel complex model systems that are human-relevant and readily available are urgently required. Here, we report the development of a human immunocompetent Choroid-on-Chip (CoC), a human cell-based in vitro model of the choroid layer of the eye integrating melanocytes and microvascular endothelial cells, covered by a layer of retinal pigmented epithelial cells. Immunocompetence is achieved by perfusion of peripheral immune cells. We demonstrate controlled immune cell recruitment into the stromal compartments through a vascular monolayer and in vivo-like cytokine release profiles. To investigate applicability for both efficacy testing of immunosuppressive compounds as well as safety profiling of immunoactivating antibodies, we exposed the CoCs to cyclosporine and tested CD3 bispecific antibodies.

scholarly journals Imaging cell biology in live animals: Ready for prime time

2013 ◽  
Vol 201 (7) ◽  
pp. 969-979 ◽  
Author(s):  
Roberto Weigert ◽  
Natalie Porat-Shliom ◽  
Panomwat Amornphimoltham
Keyword(s):  
Cell Biology ◽  
Cancer Biology ◽  
In Vitro Model ◽  
Time Lapse ◽  
Living Cells ◽  
Model Systems ◽  
Prime Time ◽  
Vitro Model

Time-lapse fluorescence microscopy is one of the main tools used to image subcellular structures in living cells. Yet for decades it has been applied primarily to in vitro model systems. Thanks to the most recent advancements in intravital microscopy, this approach has finally been extended to live rodents. This represents a major breakthrough that will provide unprecedented new opportunities to study mammalian cell biology in vivo and has already provided new insight in the fields of neurobiology, immunology, and cancer biology.

Biological Responses of Fibroblasts to Cyclic Stretching: A Novel Culture Model Study

2000 ◽  
Author(s):  
James H.-C. Wang ◽  
David Stone ◽  
Fengyan Jia ◽  
Chris Celechovsky ◽  
Savio L.-Y. Woo
Keyword(s):  
Control Cell ◽  
Model Systems ◽  
Cell Alignment ◽  
Experimental Conditions ◽  
Cyclic Stretching ◽  
Biological Responses ◽  
Model Study ◽  
Vitro Model

Abstract Because of the advantage of better control of experimental conditions, in vitro model systems have been developed to examine the effects of mechanical loading on cells. Previous studies have shown that cyclic stretching causes cells to change orientation, proliferation and gene expression (Buck et al., 1980; Wang et al., 1995; Leung et al., 1976). However, one drawback of these model systems is that they are unable to control cell alignment and shape, and in addition, some provide heterogeneous strains to cells during stretching (See review by Schaffer, 1994). Consequently, cellular responses in these systems may not be similar to those in vivo. For example, tendon and ligament fibroblasts align with collagen fibers in vivo and are hence subjected to stretching along the tissue long axis. In contrast, in many existing systems, cells either randomly orient or orient away from the stretching direction.

New Achievements in Human Cell Toxicology: The 20th Annual Workshop on In Vitro Toxicology

2003 ◽  
Vol 31 (3) ◽  
pp. 241-243
Author(s):  
Ada Kolman
Keyword(s):  
Human Cell ◽  
Toxicity Testing ◽  
Model Systems ◽  
In Vitro Toxicology ◽  
Free Paper ◽  
Mechanisms Of Toxicity ◽  
European Meeting ◽  
Vitro Model ◽  
Oral Presentations

The 20th Annual Workshop on In Vitro Toxicology (Oxford, UK, September 22–24, 2002) was convened as part of a European meeting entitled Human Cell Culture 2002. The meeting was arranged by the Scandinavian Society for Cell Toxicology (SSCT), the European Tissue Culture Society and the British Prostate Group. Two sessions, which are summarised in this report, were devoted to in vitro toxicology: Human Cell Toxicology and The SSCT Free Paper Session. Outstanding experts in the field of toxicology outlined contemporary approaches in toxicity testing in their lectures. Short oral presentations demonstrated a variety of in vitro model systems and methodologies, which can be useful for investigating human toxicity, as well as for studies on mechanisms of toxicity.

Mechanism of glucose sensing in the small intestine

2003 ◽  
Vol 31 (6) ◽  
pp. 1140-1142 ◽  
Author(s):  
J. Dyer ◽  
S. Vayro ◽  
S.P. Shirazi-Beechey
Keyword(s):  
Glucose Transporter ◽  
Glucose Sensor ◽  
Cell Function ◽  
Glucose Sensing ◽  
Model Systems ◽  
Luminal Membrane ◽  
Sense And Respond ◽  
Vitro Model

Sensing nutrients is a fundamental task for all living cells. For most eukaryotic cells glucose is a major source of energy, having significant and varied effects on cell function. Interest in identifying mechanisms by which cells sense and respond to variations in glucose concentration has increased recently. The epithelial cells lining the intestinal tract are exposed, from the luminal domain, to an environment with continuous and massive fluctuations in the levels of dietary monosaccharides. Enterocytes therefore have to sense and respond to the significant changes in the levels of luminal sugars, and regulate the expression of the intestinal glucose transporter (Na+/glucose co-transporter, SGLT1) accordingly. Our data, using a combination of in vivo and in vitro model systems, suggest that glucose in the lumen of the intestine is sensed by a glucose sensor residing on the external face of the enterocyte luminal membrane. Glucose binds to the sensor and generates an intracellular signal leading to enhancement in the expression of SGLT1. The generated signal is independent of glucose metabolism and is likely to operate via a G-protein-coupled receptor and cAMP/protein kinase A signalling cascade.

Synergy between paclitaxel plus an exogenous methyl donor in the suppression of murine demyelinating diseases

2007 ◽  
Vol 13 (5) ◽  
pp. 596-609 ◽  
Author(s):  
FG Mastronardi ◽  
H. Tsui ◽  
S. Winer ◽  
DD Wood ◽  
T. Selvanantham ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Combination Therapy ◽  
Clinical Signs ◽  
Demyelinating Diseases ◽  
Model Systems ◽  
Methyl Donor ◽  
Negative Balance ◽  
Vitro Model

Progressive demyelination in multiple sclerosis (MS) reflects the negative balance between myelin damage and repair due to physical and molecular barriers, such as astrocytic glial scars, between oligodendrocytes and target neurons. In this paper, we show that combination therapy with paclitaxel (Taxol®) plus the universal methyl-donor, vitamin B12CN (B12CN), dramatically limits progressive demyelination, and enhances remyelination in several independent, immune and nonimmune, in vivo and in vitro model systems. Combination therapy significantly reduced clinical signs of EAE in SJL mice, as well as the spontaneously demyelinating ND4 transgenic mouse. Astrocytosis was normalised in parallel to ultrastructural and biochemical evidence of remyelination. The combination therapy suppressed T cell expansion, reduced IFN-gamma, while enhancing IFN-beta and STAT-1 expression, STAT-1 phosphorylation and methylation of STAT-1 and MBP in the brain. Paclitaxel/B12CN has nearly identical effects to the previously described combination of IFN-beta/ B12CN, whose clinical usefulness is transient because of IFN-neutralising antibodies, not observed (or expected) with the present drug combination. This report provides a mechanistic foundation for the development of a new therapeutic strategy in humans with MS. Multiple Sclerosis 2007; 13: 596-609. http://msj.sagepub.com

scholarly journals Author Correction: The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nagasuryaprasad Kotikalapudi ◽  
Samuel Joshua Pragasam Sampath ◽  
Sinha Sukesh Narayan ◽  
Bhonde R. ◽  
Harishankar Nemani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Therapy ◽  
In Vitro Model ◽  
Model Systems ◽  
Mesenchymal Stem Cell Therapy ◽  
Preclinical Diabetes ◽  
Vitro Model

Morphological effects of sulfur mustard on a human skin equivalent

1991 ◽  
Vol 49 ◽  
pp. 78-79
Author(s):  
J.P. Petrali ◽  
S.B. Oglesby ◽  
T.A. Justus
Keyword(s):  
Human Skin ◽  
Sulfur Mustard ◽  
Athymic Nude Mouse ◽  
Skin Equivalent ◽  
Model Systems ◽  
Cells In Culture ◽  
Vitro Model ◽  
Human Skin Equivalent

We have previously reported morphological correlates of sulfur mustard (HD) toxicity in several model systems: the human skin grafted athymic nude mouse; the hairless guinea pig; and human cells in culture. We are now describing HD effects in a human skin equivalent, TESTSKIN®, and comparing these effects with those already reported for animal models and cells in culture. The human skin equivalent (HSE) is used here as an organotypic in vitro model system to bridge the knowledge gap between HD effects in monotypic cells in culture and animal in vivo effects. Additionally, HSE allowed study of HD toxicity which circumvented the concern of using human biopsied tissue.

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