Platelet decoys inhibit thrombosis and prevent metastatic tumor formation in preclinical models
Authors
Papa, Anne-LaureJiang, 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.
UMass Chan Affiliations
New England Center for Stroke Research, Department of RadiologyDocument Type
Journal ArticlePublication Date
2019-02-13
Metadata
Show full item recordAbstract
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.aau5898Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48345PubMed ID
30760580Related Resources
ae974a485f413a2113503eed53cd6c53
10.1126/scitranslmed.aau5898