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Sci Transl Med. 2019 Feb 13;11(479). pii: eaau5898. doi: 10.1126/scitranslmed.aau5898.

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

Author information

1
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. don.ingber@wyss.harvard.edu alpapa@gwu.edu.
2
Department of Biomedical Engineering, The George Washington University, Washington, DC 20052, USA.
3
Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
4
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
5
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
6
New England Center for Stroke Research, Department of Radiology, University of Massachusetts, Worcester, MA 01655, USA.
7
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
8
Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA 02138, USA.

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.

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