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    Platelet decoys inhibit thrombosis and prevent metastatic tumor formation in preclinical models

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    Authors
    Papa, Anne-Laure
    Jiang, Amanda
    Korin, Netanel
    Chen, Michelle B.
    Langan, Erin T.
    Waterhouse, Anna
    Nash, Emma
    Caroff, Jildaz
    Graveline, Amanda
    Vernet, Andyna
    Mammoto, Akiko
    Mammoto, Tadanori
    Jain, Abhishek
    Kamm, Roger D.
    Gounis, Matthew J.
    Ingber, Donald E.
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    UMass Chan Affiliations
    New England Center for Stroke Research, Department of Radiology
    Document Type
    Journal Article
    Publication Date
    2019-02-13
    Keywords
    Cardiovascular Diseases
    Hemic and Immune Systems
    Neoplasms
    Nervous System Diseases
    Radiology
    
    Metadata
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    Link to Full Text
    https://doi.org/10.1126/scitranslmed.aau5898
    Abstract
    Platelets are crucial for normal hemostasis; however, their hyperactivation also contributes to many potentially lethal pathologies including myocardial infarction, stroke, and cancer. We hypothesized that modified platelets lacking their aggregation and activation capacity could act as reversible inhibitors of platelet activation cascades. Here, we describe the development of detergent-extracted human modified platelets (platelet decoys) that retained platelet binding functions but were incapable of functional activation and aggregation. Platelet decoys inhibited aggregation and adhesion of platelets on thrombogenic surfaces in vitro, which could be immediately reversed by the addition of normal platelets; in vivo in a rabbit model, pretreatment with platelet decoys inhibited arterial injury-induced thromboembolism. Decoys also interfered with platelet-mediated human breast cancer cell aggregation, and their presence decreased cancer cell arrest and extravasation in a microfluidic human microvasculature on a chip. In a mouse model of metastasis, simultaneous injection of the platelet decoys with tumor cells inhibited metastatic tumor growth. Thus, our results suggest that platelet decoys might represent an effective strategy for obtaining antithrombotic and antimetastatic effects.
    Source

    Sci Transl Med. 2019 Feb 13;11(479). pii: eaau5898. doi: 10.1126/scitranslmed.aau5898. Link to article on publisher's site

    DOI
    10.1126/scitranslmed.aau5898
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/48345
    PubMed ID
    30760580
    Related Resources

    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1126/scitranslmed.aau5898
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