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  1. Artikel: Differential Monocyte Actuation in a Three-Organ Functional Innate Immune System-on-a-Chip.

    Sasserath, Trevor / Rumsey, John W / McAleer, Christopher W / Bridges, Lee Richard / Long, Christopher J / Elbrecht, Daniel / Schuler, Franz / Roth, Adrian / Bertinetti-LaPatki, Christina / Shuler, Michael L / Hickman, James J

    Advanced science (Weinheim, Baden-Wurttemberg, Germany)

    2020  Band 7, Heft 13, Seite(n) 2000323

    Abstract: A functional, human, multiorgan, pumpless, immune system-on-a-chip featuring recirculating THP-1 immune cells with cardiomyocytes, skeletal muscle, and liver in separate compartments in a serum-free medium is developed. This in vitro platform can emulate ...

    Abstract A functional, human, multiorgan, pumpless, immune system-on-a-chip featuring recirculating THP-1 immune cells with cardiomyocytes, skeletal muscle, and liver in separate compartments in a serum-free medium is developed. This in vitro platform can emulate both a targeted immune response to tissue-specific damage, and holistic proinflammatory immune response to proinflammatory compound exposure. The targeted response features fluorescently labeled THP-1 monocytes selectively infiltrating into an amiodarone-damaged cardiac module and changes in contractile force measurements without immune-activated damage to the other organ modules. In contrast to the targeted immune response, general proinflammatory treatment of immune human-on-a-chip systems with lipopolysaccharide (LPS) and interferon-
    Sprache Englisch
    Erscheinungsdatum 2020-06-02
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ZDB-ID 2808093-2
    ISSN 2198-3844
    ISSN 2198-3844
    DOI 10.1002/advs.202000323
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: Piezoelectric BioMEMS Cantilever for Measurement of Muscle Contraction and for Actuation of Mechanosensitive Cells.

    Coln, Elizabeth A / Colon, Alisha / Long, Christopher J / Sriram, Narasimhan Narasimhan / Esch, Mandy / Prot, Jean-Matthieu / Elbrecht, Daniel H / Wang, Ying / Jackson, Max / Shuler, Michael L / Hickman, James J

    MRS communications

    2019  Band 9, Heft 4, Seite(n) 1186–1192

    Abstract: A piezoelectric biomedical microelectromechanical system (bioMEMS) cantilever device was designed and fabricated to act as either a sensing element for muscle tissue contraction or as an actuator to apply mechanical force to cells. The sensing ability of ...

    Abstract A piezoelectric biomedical microelectromechanical system (bioMEMS) cantilever device was designed and fabricated to act as either a sensing element for muscle tissue contraction or as an actuator to apply mechanical force to cells. The sensing ability of the piezoelectric cantilevers was shown by monitoring the electrical signal generated from the piezoelectric aluminum nitride in response to the contraction of iPSC-derived cardiomyocytes cultured on the piezoelectric cantilevers. Actuation was demonstrated by applying electrical pulses to the piezoelectric cantilever and observing bending via an optical detection method. This piezoelectric cantilever device was designed to be incorporated into body-on-a-chip systems.
    Sprache Englisch
    Erscheinungsdatum 2019-09-20
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2645443-9
    ISSN 2159-6867 ; 2159-6859
    ISSN (online) 2159-6867
    ISSN 2159-6859
    DOI 10.1557/mrc.2019.129
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics.

    McAleer, Christopher W / Long, Christopher J / Elbrecht, Daniel / Sasserath, Trevor / Bridges, L Richard / Rumsey, John W / Martin, Candace / Schnepper, Mark / Wang, Ying / Schuler, Franz / Roth, Adrian B / Funk, Christoph / Shuler, Michael L / Hickman, James J

    Science translational medicine

    2019  Band 11, Heft 497

    Abstract: A pumpless, reconfigurable, multi-organ-on-a-chip system containing recirculating serum-free medium can be used to predict preclinical on-target efficacy, metabolic conversion, and measurement of off-target toxicity of drugs using functional biological ... ...

    Abstract A pumpless, reconfigurable, multi-organ-on-a-chip system containing recirculating serum-free medium can be used to predict preclinical on-target efficacy, metabolic conversion, and measurement of off-target toxicity of drugs using functional biological microelectromechanical systems. In the first configuration of the system, primary human hepatocytes were cultured with two cancer-derived human bone marrow cell lines for antileukemia drug analysis in which diclofenac and imatinib demonstrated a cytostatic effect on bone marrow cancer proliferation. Liver viability was not affected by imatinib; however, diclofenac reduced liver viability by 30%. The second configuration housed a multidrug-resistant vulva cancer line, a non-multidrug-resistant breast cancer line, primary hepatocytes, and induced pluripotent stem cell-derived cardiomyocytes. Tamoxifen reduced viability of the breast cancer cells only after metabolite generation but did not affect the vulva cancer cells except when coadministered with verapamil, a permeability glycoprotein inhibitor. Both tamoxifen alone and coadministration with verapamil produced off-target cardiac effects as indicated by a reduction of contractile force, beat frequency, and conduction velocity but did not affect viability. These systems demonstrate the utility of a human cell-based in vitro culture system to evaluate both on-target efficacy and off-target toxicity for parent drugs and their metabolites; these systems can augment and reduce the use of animals and increase the efficiency of drug evaluations in preclinical studies.
    Mesh-Begriff(e) Antineoplastic Agents/pharmacology ; Cell Proliferation/drug effects ; Cells, Cultured ; Diclofenac/pharmacology ; Drug Evaluation, Preclinical/methods ; Humans ; Imatinib Mesylate/pharmacology ; Lab-On-A-Chip Devices ; Tamoxifen/pharmacology ; Verapamil/pharmacology
    Chemische Substanzen Antineoplastic Agents ; Tamoxifen (094ZI81Y45) ; Diclofenac (144O8QL0L1) ; Imatinib Mesylate (8A1O1M485B) ; Verapamil (CJ0O37KU29)
    Sprache Englisch
    Erscheinungsdatum 2019-04-25
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.aav1386
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel: Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system

    Oleaga, Carlota / Riu, Anne / Rothemund, Sandra / Lavado, Andrea / McAleer, Christopher W / Long, Christopher J / Persaud, Keisha / Narasimhan, Narasimhan Sriram / Tran, My / Roles, Jeffry / Carmona-Moran, Carlos A / Sasserath, Trevor / Elbrecht, Daniel H / Kumanchik, Lee / Bridges, L. Richard / Martin, Candace / Schnepper, Mark T / Ekman, Gail / Jackson, Max /
    Wang, Ying I / Note, Reine / Langer, Jessica / Teissier, Silvia / Hickman, James J

    Biomaterials. 2018 Nov., v. 182

    2018  

    Abstract: Regulation of cosmetic testing and poor predictivity of preclinical drug studies has spurred efforts to develop new methods for systemic toxicity. Current in vitro assays do not fully represent physiology, often lacking xenobiotic metabolism. Functional ... ...

    Abstract Regulation of cosmetic testing and poor predictivity of preclinical drug studies has spurred efforts to develop new methods for systemic toxicity. Current in vitro assays do not fully represent physiology, often lacking xenobiotic metabolism. Functional human multi-organ systems containing iPSC derived cardiomyocytes and primary hepatocytes were maintained under flow using a low-volume pumpless system in a serum-free medium. The functional readouts for contractile force and electrical conductivity enabled the non-invasive study of cardiac function. The presence of the hepatocytes in the system induced cardiotoxic effects from cyclophosphamide and reduced them for terfenadine due to drug metabolism, as expected from each compound's pharmacology. A computational fluid dynamics simulation enabled the prediction of terfenadine-fexofenadine pharmacokinetics, which was validated by HPLC-MS. This in vitro platform recapitulates primary aspects of the in vivo crosstalk between heart and liver and enables pharmacological studies, involving both organs in a single in vitro platform. The system enables non-invasive readouts of cardiotoxicity of drugs and their metabolites. Hepatotoxicity can also be evaluated by biomarker analysis and change in metabolic function. Integration of metabolic function in toxicology models can improve adverse effects prediction in preclinical studies and this system could also be used for chronic studies as well.
    Schlagwörter adverse effects ; biochemical pathways ; biomarkers ; cardiac output ; cardiomyocytes ; cosmetics testing ; cyclophosphamide ; electrical conductivity ; fluid mechanics ; hepatocytes ; hepatotoxicity ; high performance liquid chromatography ; humans ; in vitro studies ; liver ; mass spectrometry ; metabolites ; models ; organ-on-a-chip ; pharmacokinetics ; prediction ; toxicology ; xenobiotics
    Sprache Englisch
    Erscheinungsverlauf 2018-11
    Umfang p. 176-190.
    Erscheinungsort Elsevier Ltd
    Dokumenttyp Artikel
    ZDB-ID 603079-8
    ISSN 0142-9612
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2018.07.062
    Datenquelle NAL Katalog (AGRICOLA)

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  5. Artikel ; Online: Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system.

    Oleaga, Carlota / Riu, Anne / Rothemund, Sandra / Lavado, Andrea / McAleer, Christopher W / Long, Christopher J / Persaud, Keisha / Narasimhan, Narasimhan Sriram / Tran, My / Roles, Jeffry / Carmona-Moran, Carlos A / Sasserath, Trevor / Elbrecht, Daniel H / Kumanchik, Lee / Bridges, L Richard / Martin, Candace / Schnepper, Mark T / Ekman, Gail / Jackson, Max /
    Wang, Ying I / Note, Reine / Langer, Jessica / Teissier, Silvia / Hickman, James J

    Biomaterials

    2018  Band 182, Seite(n) 176–190

    Abstract: Regulation of cosmetic testing and poor predictivity of preclinical drug studies has spurred efforts to develop new methods for systemic toxicity. Current in vitro assays do not fully represent physiology, often lacking xenobiotic metabolism. Functional ... ...

    Abstract Regulation of cosmetic testing and poor predictivity of preclinical drug studies has spurred efforts to develop new methods for systemic toxicity. Current in vitro assays do not fully represent physiology, often lacking xenobiotic metabolism. Functional human multi-organ systems containing iPSC derived cardiomyocytes and primary hepatocytes were maintained under flow using a low-volume pumpless system in a serum-free medium. The functional readouts for contractile force and electrical conductivity enabled the non-invasive study of cardiac function. The presence of the hepatocytes in the system induced cardiotoxic effects from cyclophosphamide and reduced them for terfenadine due to drug metabolism, as expected from each compound's pharmacology. A computational fluid dynamics simulation enabled the prediction of terfenadine-fexofenadine pharmacokinetics, which was validated by HPLC-MS. This in vitro platform recapitulates primary aspects of the in vivo crosstalk between heart and liver and enables pharmacological studies, involving both organs in a single in vitro platform. The system enables non-invasive readouts of cardiotoxicity of drugs and their metabolites. Hepatotoxicity can also be evaluated by biomarker analysis and change in metabolic function. Integration of metabolic function in toxicology models can improve adverse effects prediction in preclinical studies and this system could also be used for chronic studies as well.
    Mesh-Begriff(e) Cardiotoxicity/etiology ; Cell Line ; Cells, Cultured ; Coculture Techniques/instrumentation ; Cyclophosphamide/metabolism ; Cyclophosphamide/toxicity ; Drug Evaluation, Preclinical/instrumentation ; Equipment Design ; Hepatocytes/cytology ; Hepatocytes/drug effects ; Hepatocytes/metabolism ; Histamine H1 Antagonists, Non-Sedating/metabolism ; Histamine H1 Antagonists, Non-Sedating/toxicity ; Humans ; Immunosuppressive Agents/metabolism ; Immunosuppressive Agents/toxicity ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/drug effects ; Induced Pluripotent Stem Cells/metabolism ; Lab-On-A-Chip Devices ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/metabolism ; Terfenadine/metabolism ; Terfenadine/toxicity
    Chemische Substanzen Histamine H1 Antagonists, Non-Sedating ; Immunosuppressive Agents ; Terfenadine (7BA5G9Y06Q) ; Cyclophosphamide (8N3DW7272P)
    Sprache Englisch
    Erscheinungsdatum 2018-08-04
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2018.07.062
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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