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1,739 results on '"Werner, Carsten"'

7. Nerve growth factor receptor (Ngfr) induces neurogenic plasticity by suppressing reactive astroglial Lcn2/Slc22a17 signaling in Alzheimer’s disease

Author

Siddiqui, Tohid, Cosacak, Mehmet Ilyas, Popova, Stanislava, Bhattarai, Prabesh, Yilmaz, Elanur, Lee, Annie J., Min, Yuhao, Wang, Xue, Allen, Mariet, İş, Özkan, Atasavum, Zeynep Tansu, Rodriguez-Muela, Natalia, Vardarajan, Badri N., Flaherty, Delaney, Teich, Andrew F., Santa-Maria, Ismael, Freudenberg, Uwe, Werner, Carsten, Tosto, Giuseppe, Mayeux, Richard, Ertekin-Taner, Nilüfer, and Kizil, Caghan

Published
2023
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11. A customizable microfluidic platform for medium-throughput modeling of neuromuscular circuits

Author

Bellmann, Jessica, Goswami, Ruchi Y, Girardo, Salvatore, Rein, Nelly, Hosseinzadeh, Zohreh, Hicks, Michael R, Busskamp, Volker, Pyle, April D, Werner, Carsten, and Sterneckert, Jared

Subjects
Rare Diseases, Stem Cell Research, Biotechnology, Neurosciences, Neurological, Good Health and Well Being, Cell Adhesion, Cell Differentiation, Cells, Cultured, Dimethylpolysiloxanes, Humans, Induced Pluripotent Stem Cells, Laminin, Maleates, Microfluidics, Motor Neurons, Muscle Fibers, Skeletal, Neuromuscular Junction, Peptides, Plasma Gases, Polyethylenes, poly(ethylene-alt-maleic anhydride), Neuromuscular circuit, Skeletal muscle, Rabies viral tracing, Motor unit
Abstract

Neuromuscular circuits (NMCs) are vital for voluntary movement, and effective models of NMCs are needed to understand the pathogenesis of, as well as to identify effective treatments for, multiple diseases, including Duchenne's muscular dystrophy and amyotrophic lateral sclerosis. Microfluidics are ideal for recapitulating the central and peripheral compartments of NMCs, but myotubes often detach before functional NMCs are formed. In addition, microfluidic systems are often limited to a single experimental unit, which significantly limits their application in disease modeling and drug discovery. Here, we developed a microfluidic platform (MFP) containing over 100 experimental units, making it suitable for medium-throughput applications. To overcome detachment, we incorporated a reactive polymer surface allowing customization of the environment to culture different cell types. Using this approach, we identified conditions that enable long-term co-culture of human motor neurons and myotubes differentiated from human induced pluripotent stem cells inside our MFP. Optogenetics demonstrated the formation of functional NMCs. Furthermore, we developed a novel application of the rabies tracing assay to efficiently identify NMCs in our MFP. Therefore, our MFP enables large-scale generation and quantification of functional NMCs for disease modeling and pharmacological drug targeting.

Published
2019

13. A modular in vitro flow model to analyse blood-surface interactions under physiological conditions

Author

Valtin Juliane, Behrens Stephan, Maitz Manfred F., Schmieder Florian, Sonntag Frank, and Werner Carsten

Subjects
hemocompatibility, in vitro flow model, bloodsurface interactions, Medicine
Abstract

Newly developed materials for blood-contacting devices need to undergo hemocompatibility testing to prove compliance with clinical requirements. However, many current in vitro models disregard the influence of flow conditions and blood exchange as it occurs in vivo. Here, we present a flow model which allows testing of blood-surface interactions under more physiological conditions. This modular platform consists of a triple-pump-chip and a microchannel-chip with a customizable surface. Flow conditions can be adjusted individually within the physiological range. A performance test with whole blood confirmed the hemocompatibility of our modular platform. Hemolysis was negligible, inflammation and hemostasis parameters were comparable to those detected in a previously established quasi-static whole blood screening chamber. The steady supply of fresh blood avoids secondary effects by nonphysiological accumulation of activation products. Experiments with three subsequently tested biomaterials showed results similar to literature and our own experience. The reported results suggest that our developed flow model allows the evaluation of blood-contacting materials under physiological flow conditions. By adjusting the occurring wall shear stress, the model can be adapted for selected test conditions.

Published
2021
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22. The Influence of Sulfation Degree of Glycosaminoglycan-Functionalized 3D Collagen I Networks on Cytokine Profiles of In Vitro Macrophage–Fibroblast Cocultures.

Author

Ullm, Franziska, Renner, Alexander, Freudenberg, Uwe, Werner, Carsten, and Pompe, Tilo

Subjects
SULFATION, GLYCOSAMINOGLYCANS, COLLAGEN, MACROPHAGES, FIBROBLASTS
Abstract

Cell–cell interactions between fibroblasts and immune cells, like macrophages, are influenced by interaction with the surrounding extracellular matrix during wound healing. In vitro hydrogel models that mimic and modulate these interactions, especially of soluble mediators like cytokines, may allow for a more detailed investigation of immunomodulatory processes. In the present study, a biomimetic extracellular matrix model based on fibrillar 3D collagen I networks with a functionalization with heparin or 6-ON-desulfated heparin, as mimics of naturally occurring heparan sulfate, was developed to modulate cytokine binding effects with the hydrogel matrix. The constitution and microstructure of the collagen I network were found to be stable throughout the 7-day culture period. A coculture study of primary human fibroblasts/myofibroblasts and M-CSF-stimulated macrophages was used to show its applicability to simulate processes of progressed wound healing. The quantification of secreted cytokines (IL-8, IL-10, IL-6, FGF-2) in the cell culture supernatant demonstrated the differential impact of glycosaminoglycan functionalization of the collagen I network. Most prominently, IL-6 and FGF-2 were shown to be regulated by the cell culture condition and network constitution, indicating changes in paracrine and autocrine cell–cell communication of the fibroblast–macrophage coculture. From this perspective, we consider our newly established in vitro hydrogel model suitable for mechanistic coculture analyses of primary human cells to unravel the role of extracellular matrix factors in key events of tissue regeneration and beyond. [ABSTRACT FROM AUTHOR]

Published
2024
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39. 3D Culture Method for Alzheimer's Disease Modeling Reveals Interleukin-4 Rescues Aβ42-Induced Loss of Human Neural Stem Cell Plasticity

Author

Papadimitriou, Christos, Celikkaya, Hilal, Cosacak, Mehmet I., Mashkaryan, Violeta, Bray, Laura, Bhattarai, Prabesh, Brandt, Kerstin, Hollak, Heike, Chen, Xin, He, Shuijin, Antos, Christopher L., Lin, Weilin, Thomas, Alvin Kuriakose, Dahl, Andreas, Kurth, Thomas, Friedrichs, Jens, Zhang, Yixin, Freudenberg, Uwe, Werner, Carsten, and Kizil, Caghan

Published
2018
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