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  1. Book ; Thesis: Mikrophysiologische Zellkulturmodelle der Leber und der Blut-Hirn-Schranke

    Mosig, Alexander S.

    2017  

    Author's details von Dr. rer. nat. Alexander S. Mosig
    Language German ; English
    Size 1 Band (verschiedene Seitenzählungen), Illustrationen, Diagramme
    Publishing place Jena
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Habilitationsschrift, Friedrich-Schiller-Universität Jena, 2017
    Note Enthält Beiträge aus verschiedenen Zeitschriften
    HBZ-ID HT019446029
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    2017 E 1480 order for loan Magazin

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  2. Book ; Thesis: Dissection of immune-response and pathogene-host interaction of E. coli and S. aureus in the liver-on-chip

    Carlstedt, Swen / Löffler, Bettina / Mosig, Alexander S. / Loskill, Peter

    2021  

    Institution Friedrich-Schiller-Universität Jena
    Author's details von M. Sc. Swen Carlstedt
    Keywords Leber ; Makrophage ; Cytokine
    Subject Zytokine ; Makrozyt ; Makrocyt ; Makrophagen ; Hepar ; Lebergewebe ; Leberparenchym
    Language English ; German
    Size XIV, 98, a-q Seiten, Illustrationen, Diagramme, 29,5 cm
    Publishing place Jena
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Dissertation, Friedrich-Schiller-Universität Jena, 2021
    Note Zusammenfassungen in deutscher und englischer Sprache ; Tag der Verteidigung: 20.04.2021
    HBZ-ID HT021003369
    Database Catalogue ZB MED Medicine, Health

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  3. Article ; Online: Tailoring the Degradation Time of Polycationic PEG-Based Hydrogels toward Dynamic Cell Culture Matrices.

    Kowalczuk, Kathrin / Wegner, Valentin D / Mosig, Alexander S / Schacher, Felix H

    ACS applied bio materials

    2024  Volume 7, Issue 4, Page(s) 2402–2412

    Abstract: Poly(ethylene glycol)-based (PEG) hydrogels provide an ideal platform to obtain well-defined and tailor-made cell culture matrices to ... ...

    Abstract Poly(ethylene glycol)-based (PEG) hydrogels provide an ideal platform to obtain well-defined and tailor-made cell culture matrices to enhance
    MeSH term(s) Tissue Engineering/methods ; Biocompatible Materials ; Cell Culture Techniques ; Collagen ; Hydrogels/pharmacology ; Hydrogels/chemistry
    Chemical Substances Biocompatible Materials ; Collagen (9007-34-5) ; Hydrogels
    Language English
    Publishing date 2024-03-12
    Publishing country United States
    Document type Journal Article
    ISSN 2576-6422
    ISSN (online) 2576-6422
    DOI 10.1021/acsabm.4c00057
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Functional integration of natural killer cells in a microfluidically perfused liver on-a-chip model.

    Fahrner, René / Gröger, Marko / Settmacher, Utz / Mosig, Alexander S

    BMC research notes

    2023  Volume 16, Issue 1, Page(s) 285

    Abstract: Objective: The liver acts as an innate immunity-dominant organ and natural killer (NK) cells, are the main lymphocyte population in the human liver. NK cells are in close interaction with other immune cells, acting as the first line of defense against ... ...

    Abstract Objective: The liver acts as an innate immunity-dominant organ and natural killer (NK) cells, are the main lymphocyte population in the human liver. NK cells are in close interaction with other immune cells, acting as the first line of defense against pathogens, infections, and injury. A previously developed, three-dimensional, perfused liver-on-a-chip comprised of human cells was used to integrate NK cells, representing pivotal immune cells during liver injury and regeneration. The objective of this study was to integrate functional NK cells in an in vitro model of the human liver and assess utilization of the model for NK cell-dependent studies of liver inflammation.
    Results: NK cells from human blood and liver specimen were isolated by Percoll separation with subsequent magnetic cell separation (MACS), yielding highly purified blood and liver derived NK cells. After stimulation with toll-like-receptor (TLR) agonists (lipopolysaccharides, Pam3CSK4), isolated NK cells showed increased interferon (IFN)-gamma secretion. To study the role of NK cells in a complex hepatic environment, these cells were integrated in the vascular compartment of a microfluidically supported liver-on-a-chip model in close interaction with endothelial and resident macrophages. Successful, functional integration of NK cells was verified by immunofluorescence staining (NKp46), flow cytometry analysis and TLR agonist-dependent secretion of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. Lastly, we observed that inflammatory activation of NK cells in the liver-on-a-chip led to a loss of vascular barrier integrity. Overall, our data shows the first successful, functional integration of NK cells in a liver-on-a-chip model that can be utilized to investigate NK cell-dependent effects on liver inflammation in vitro.
    MeSH term(s) Humans ; Interferon-gamma ; Killer Cells, Natural ; Liver ; Tumor Necrosis Factor-alpha ; Inflammation ; Lab-On-A-Chip Devices
    Chemical Substances Interferon-gamma (82115-62-6) ; Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2023-10-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2413336-X
    ISSN 1756-0500 ; 1756-0500
    ISSN (online) 1756-0500
    ISSN 1756-0500
    DOI 10.1186/s13104-023-06575-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Organ-on-chip models: new opportunities for biomedical research.

    Mosig, Alexander S

    Future science OA

    2016  Volume 3, Issue 2, Page(s) FSO130

    Language English
    Publishing date 2016-07-06
    Publishing country England
    Document type Editorial
    ISSN 2056-5623
    ISSN 2056-5623
    DOI 10.4155/fsoa-2016-0038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Organ-on-chip models for infectious disease research.

    Alonso-Roman, Raquel / Mosig, Alexander S / Figge, Marc Thilo / Papenfort, Kai / Eggeling, Christian / Schacher, Felix H / Hube, Bernhard / Gresnigt, Mark S

    Nature microbiology

    2024  Volume 9, Issue 4, Page(s) 891–904

    Abstract: Research on microbial pathogens has traditionally relied on animal and cell culture models to mimic infection processes in the host. Over recent years, developments in microfluidics and bioengineering have led to organ-on-chip (OoC) technologies. These ... ...

    Abstract Research on microbial pathogens has traditionally relied on animal and cell culture models to mimic infection processes in the host. Over recent years, developments in microfluidics and bioengineering have led to organ-on-chip (OoC) technologies. These microfluidic systems create conditions that are more physiologically relevant and can be considered humanized in vitro models. Here we review various OoC models and how they have been applied for infectious disease research. We outline the properties that make them valuable tools in microbiology, such as dynamic microenvironments, vascularization, near-physiological tissue constitutions and partial integration of functional immune cells, as well as their limitations. Finally, we discuss the prospects for OoCs and their potential role in future infectious disease research.
    MeSH term(s) Animals ; Microfluidics ; Communicable Diseases
    Language English
    Publishing date 2024-03-25
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-024-01645-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Functional integration of natural killer cells in a microfluidically perfused liver on-a-chip model

    René Fahrner / Marko Gröger / Utz Settmacher / Alexander S. Mosig

    BMC Research Notes, Vol 16, Iss 1, Pp 1-

    2023  Volume 8

    Abstract: Abstract Objective The liver acts as an innate immunity-dominant organ and natural killer (NK) cells, are the main lymphocyte population in the human liver. NK cells are in close interaction with other immune cells, acting as the first line of defense ... ...

    Abstract Abstract Objective The liver acts as an innate immunity-dominant organ and natural killer (NK) cells, are the main lymphocyte population in the human liver. NK cells are in close interaction with other immune cells, acting as the first line of defense against pathogens, infections, and injury. A previously developed, three-dimensional, perfused liver-on-a-chip comprised of human cells was used to integrate NK cells, representing pivotal immune cells during liver injury and regeneration. The objective of this study was to integrate functional NK cells in an in vitro model of the human liver and assess utilization of the model for NK cell-dependent studies of liver inflammation. Results NK cells from human blood and liver specimen were isolated by Percoll separation with subsequent magnetic cell separation (MACS), yielding highly purified blood and liver derived NK cells. After stimulation with toll-like-receptor (TLR) agonists (lipopolysaccharides, Pam3CSK4), isolated NK cells showed increased interferon (IFN)-gamma secretion. To study the role of NK cells in a complex hepatic environment, these cells were integrated in the vascular compartment of a microfluidically supported liver-on-a-chip model in close interaction with endothelial and resident macrophages. Successful, functional integration of NK cells was verified by immunofluorescence staining (NKp46), flow cytometry analysis and TLR agonist-dependent secretion of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. Lastly, we observed that inflammatory activation of NK cells in the liver-on-a-chip led to a loss of vascular barrier integrity. Overall, our data shows the first successful, functional integration of NK cells in a liver-on-a-chip model that can be utilized to investigate NK cell-dependent effects on liver inflammation in vitro.
    Keywords Natural killer cells ; NKp46 ; Liver ; Microfluidic ; Liver-on-a-chip ; Cytokines ; Medicine ; R ; Biology (General) ; QH301-705.5 ; Science (General) ; Q1-390
    Subject code 610
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: An Organ-on-Chip Platform for Simulating Drug Metabolism Along the Gut-Liver Axis.

    Lucchetti, Mara / Aina, Kehinde Oluwasegun / Grandmougin, Léa / Jäger, Christian / Pérez Escriva, Pau / Letellier, Elisabeth / Mosig, Alexander S / Wilmes, Paul

    Advanced healthcare materials

    2024  , Page(s) e2303943

    Abstract: ... to tandem mass spectrometry (LC-MS/MS), irinotecan metabolites are tracked, confirming the platform's ability to represent ...

    Abstract The human microbiome significantly influences drug metabolism through the gut-liver axis, leading to modified drug responses and potential toxicity. Due to the complex nature of the human gut environment, the understanding of microbiome-driven impacts on these processes is limited. To address this, a multiorgan-on-a-chip (MOoC) platform that combines the human microbial-crosstalk (HuMiX) gut-on-chip (GoC) and the Dynamic42 liver-on-chip (LoC), mimicking the bidirectional interconnection between the gut and liver known as the gut-liver axis, is introduced. This platform supports the viability and functionality of intestinal and liver cells. In a proof-of-concept study, the metabolism of irinotecan, a widely used colorectal cancer drug, is imitated within the MOoC. Utilizing liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), irinotecan metabolites are tracked, confirming the platform's ability to represent drug metabolism along the gut-liver axis. Further, using the authors' gut-liver platform, it is shown that the colorectal cancer-associated gut bacterium, Escherichia coli, modifies irinotecan metabolism through the transformation of its inactive metabolite SN-38G into its toxic metabolite SN-38. This platform serves as a robust tool for investigating the intricate interplay between gut microbes and pharmaceuticals, offering a representative alternative to animal models and providing novel drug development strategies.
    Language English
    Publishing date 2024-03-07
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2649576-4
    ISSN 2192-2659 ; 2192-2640
    ISSN (online) 2192-2659
    ISSN 2192-2640
    DOI 10.1002/adhm.202303943
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  9. Article ; Online: Short chain fatty acids: key regulators of the local and systemic immune response in inflammatory diseases and infections.

    Ney, Lisa-Marie / Wipplinger, Maximilian / Grossmann, Martha / Engert, Nicole / Wegner, Valentin D / Mosig, Alexander S

    Open biology

    2023  Volume 13, Issue 3, Page(s) 230014

    Abstract: The human intestinal microbiome substantially affects human health and resistance to infections in its dynamic composition and varying release of microbial-derived metabolites. Short-chain fatty acids (SCFA) produced by commensal bacteria through ... ...

    Abstract The human intestinal microbiome substantially affects human health and resistance to infections in its dynamic composition and varying release of microbial-derived metabolites. Short-chain fatty acids (SCFA) produced by commensal bacteria through fermentation of indigestible fibres are considered key regulators in orchestrating the host immune response to microbial colonization by regulating phagocytosis, chemokine and central signalling pathways of cell growth and apoptosis, thereby shaping the composition and functionality of the intestinal epithelial barrier. Although research of the last decades provided valuable insight into the pleiotropic functions of SCFAs and their capability to maintain human health, mechanistic details on how SCFAs act across different cell types and other organs are not fully understood. In this review, we provide an overview of the various functions of SCFAs in regulating cellular metabolism, emphasizing the orchestration of the immune response along the gut-brain, the gut-lung and the gut-liver axes. We discuss their potential pharmacological use in inflammatory diseases and infections and highlight new options of relevant human three-dimensional organ models to investigate and validate their biological functions in more detail.
    MeSH term(s) Humans ; Fatty Acids, Volatile/metabolism ; Signal Transduction ; Brain/metabolism ; Gastrointestinal Microbiome ; Bacteria/metabolism
    Chemical Substances Fatty Acids, Volatile
    Language English
    Publishing date 2023-03-29
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2630944-0
    ISSN 2046-2441 ; 2046-2441
    ISSN (online) 2046-2441
    ISSN 2046-2441
    DOI 10.1098/rsob.230014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Evaluation of drug-induced liver toxicity of trovafloxacin and levofloxacin in a human microphysiological liver model.

    Kaden, Tim / Graf, Katja / Rennert, Knut / Li, Ruoya / Mosig, Alexander S / Raasch, Martin

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 13338

    Abstract: Drug-induced liver injury induced by already approved substances is a major threat to human patients, potentially resulting in drug withdrawal and substantial loss of financial resources in the pharmaceutical industry. Trovafloxacin, a broad-spectrum ... ...

    Abstract Drug-induced liver injury induced by already approved substances is a major threat to human patients, potentially resulting in drug withdrawal and substantial loss of financial resources in the pharmaceutical industry. Trovafloxacin, a broad-spectrum fluoroquinolone, was found to have unexpected side effects of severe hepatotoxicity, which was not detected by preclinical testing. To address the limitations of current drug testing strategies mainly involving 2D cell cultures and animal testing, a three-dimensional microphysiological model of the human liver containing expandable human liver sinusoidal endothelial cells, monocyte-derived macrophages and differentiated HepaRG cells was utilized to investigate the toxicity of trovafloxacin and compared it to the structurally-related non-toxic drug levofloxacin. In the model, trovafloxacin elicited vascular and hepatocellular toxicity associated with pro-inflammatory cytokine release already at clinically relevant concentrations, whereas levofloxacin did not provoke tissue injury. Similar to in vivo, cytokine secretion was dependent on a multicellular immune response, highlighting the potential of the complex microphysiological liver model for reliably detecting drug-related cytotoxicity in preclinical testing. Moreover, hepatic glutathione depletion and mitochondrial ROS formation were elucidated as intrinsic toxicity mechanisms contributing to trovafloxacin toxicity.
    MeSH term(s) Animals ; Humans ; Levofloxacin/toxicity ; Endothelial Cells ; Hepatitis ; Fluoroquinolones/toxicity ; Drug-Related Side Effects and Adverse Reactions ; Cytokines
    Chemical Substances trovafloxacin (9F388J00UK) ; Levofloxacin (6GNT3Y5LMF) ; Fluoroquinolones ; Cytokines
    Language English
    Publishing date 2023-08-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-40004-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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