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  1. Buch ; Dissertation / Habilitation: Mikrophysiologische Zellkulturmodelle der Leber und der Blut-Hirn-Schranke

    Mosig, Alexander S.

    2017  

    Verfasserangabe von Dr. rer. nat. Alexander S. Mosig
    Sprache Deutsch ; Englisch
    Umfang 1 Band (verschiedene Seitenzählungen), Illustrationen, Diagramme
    Erscheinungsort Jena
    Erscheinungsland Deutschland
    Dokumenttyp Buch ; Dissertation / Habilitation
    Dissertation / Habilitation Habilitationsschrift, Friedrich-Schiller-Universität Jena, 2017
    Anmerkung Enthält Beiträge aus verschiedenen Zeitschriften
    HBZ-ID HT019446029
    Datenquelle Katalog ZB MED Medizin, Gesundheit

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  2. Buch ; Dissertation / Habilitation: 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  

    Körperschaft Friedrich-Schiller-Universität Jena
    Verfasserangabe von M. Sc. Swen Carlstedt
    Schlagwörter Leber ; Makrophage ; Cytokine
    Schlagwörter Zytokine ; Makrozyt ; Makrocyt ; Makrophagen ; Hepar ; Lebergewebe ; Leberparenchym
    Sprache Englisch ; Deutsch
    Umfang XIV, 98, a-q Seiten, Illustrationen, Diagramme, 29,5 cm
    Erscheinungsort Jena
    Erscheinungsland Deutschland
    Dokumenttyp Buch ; Dissertation / Habilitation
    Dissertation / Habilitation Dissertation, Friedrich-Schiller-Universität Jena, 2021
    Anmerkung Zusammenfassungen in deutscher und englischer Sprache ; Tag der Verteidigung: 20.04.2021
    HBZ-ID HT021003369
    Datenquelle Katalog ZB MED Medizin, Gesundheit

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  3. Artikel ; 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  Band 7, Heft 4, Seite(n) 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-Begriff(e) Tissue Engineering/methods ; Biocompatible Materials ; Cell Culture Techniques ; Collagen ; Hydrogels/pharmacology ; Hydrogels/chemistry
    Chemische Substanzen Biocompatible Materials ; Collagen (9007-34-5) ; Hydrogels
    Sprache Englisch
    Erscheinungsdatum 2024-03-12
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2576-6422
    ISSN (online) 2576-6422
    DOI 10.1021/acsabm.4c00057
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; 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  Band 16, Heft 1, Seite(n) 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-Begriff(e) Humans ; Interferon-gamma ; Killer Cells, Natural ; Liver ; Tumor Necrosis Factor-alpha ; Inflammation ; Lab-On-A-Chip Devices
    Chemische Substanzen Interferon-gamma (82115-62-6) ; Tumor Necrosis Factor-alpha
    Sprache Englisch
    Erscheinungsdatum 2023-10-21
    Erscheinungsland England
    Dokumenttyp 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
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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

    Mosig, Alexander S

    Future science OA

    2016  Band 3, Heft 2, Seite(n) FSO130

    Sprache Englisch
    Erscheinungsdatum 2016-07-06
    Erscheinungsland England
    Dokumenttyp Editorial
    ISSN 2056-5623
    ISSN 2056-5623
    DOI 10.4155/fsoa-2016-0038
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; 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  Band 9, Heft 4, Seite(n) 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-Begriff(e) Animals ; Microfluidics ; Communicable Diseases
    Sprache Englisch
    Erscheinungsdatum 2024-03-25
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ISSN 2058-5276
    ISSN (online) 2058-5276
    DOI 10.1038/s41564-024-01645-6
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; 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  Band 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.
    Schlagwörter Natural killer cells ; NKp46 ; Liver ; Microfluidic ; Liver-on-a-chip ; Cytokines ; Medicine ; R ; Biology (General) ; QH301-705.5 ; Science (General) ; Q1-390
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2023-10-01T00:00:00Z
    Verlag BMC
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response.

    Ehle, Charlotte / Iyer-Bierhoff, Aishwarya / Wu, Yunchen / Xing, Shaojun / Kiehntopf, Michael / Mosig, Alexander S / Godmann, Maren / Heinzel, Thorsten

    Communications biology

    2024  Band 7, Heft 1, Seite(n) 589

    Abstract: The hepatic acute-phase response is characterized by a massive upregulation of serum proteins, such as haptoglobin and serum amyloid A, at the expense of liver homeostatic functions. Although the transcription factor hepatocyte nuclear factor 4 alpha ( ... ...

    Abstract The hepatic acute-phase response is characterized by a massive upregulation of serum proteins, such as haptoglobin and serum amyloid A, at the expense of liver homeostatic functions. Although the transcription factor hepatocyte nuclear factor 4 alpha (HNF4A) has a well-established role in safeguarding liver function and its cistrome spans around 50% of liver-specific genes, its role in the acute-phase response has received little attention so far. We demonstrate that HNF4A binds to and represses acute-phase genes under basal conditions. The reprogramming of hepatic transcription during inflammation necessitates loss of HNF4A function to allow expression of acute-phase genes while liver homeostatic genes are repressed. In a pre-clinical liver organoid model overexpression of HNF4A maintained liver functionality in spite of inflammation-induced cell damage. Conversely, HNF4A overexpression potently impaired the acute-phase response by retaining chromatin at regulatory regions of acute-phase genes inaccessible to transcription. Taken together, our data extend the understanding of dual HNF4A action as transcriptional activator and repressor, establishing HNF4A as gatekeeper for the hepatic acute-phase response.
    Mesh-Begriff(e) Hepatocyte Nuclear Factor 4/metabolism ; Hepatocyte Nuclear Factor 4/genetics ; Acute-Phase Reaction/genetics ; Acute-Phase Reaction/metabolism ; Animals ; Liver/metabolism ; Transcriptome ; Mice ; Down-Regulation ; Humans ; Mice, Inbred C57BL ; Male ; Gene Expression Regulation
    Chemische Substanzen HNF4A protein, human ; Hnf4a protein, mouse
    Sprache Englisch
    Erscheinungsdatum 2024-05-16
    Erscheinungsland England
    Dokumenttyp Journal Article
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-024-06288-1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; 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  , Seite(n) 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.
    Sprache Englisch
    Erscheinungsdatum 2024-03-07
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ZDB-ID 2649576-4
    ISSN 2192-2659 ; 2192-2640
    ISSN (online) 2192-2659
    ISSN 2192-2640
    DOI 10.1002/adhm.202303943
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; 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  Band 13, Heft 3, Seite(n) 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-Begriff(e) Humans ; Fatty Acids, Volatile/metabolism ; Signal Transduction ; Brain/metabolism ; Gastrointestinal Microbiome ; Bacteria/metabolism
    Chemische Substanzen Fatty Acids, Volatile
    Sprache Englisch
    Erscheinungsdatum 2023-03-29
    Erscheinungsland England
    Dokumenttyp 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
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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