Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Department of Biomedical Engineering, The George Washington University, Washington, DC 20052, USA.
Sci Transl Med. 2019 Feb 13;11(479). doi: 10.1126/scitranslmed.aau5898.
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.
血小板对于正常止血至关重要；然而，它们的过度激活也会导致许多潜在的致命病理情况，包括心肌梗死、中风和癌症。我们假设，缺乏聚集和激活能力的修饰血小板可以作为血小板激活级联的可逆抑制剂。在这里，我们描述了去污剂提取的人修饰血小板（血小板诱饵）的开发，该血小板保留了血小板结合功能，但不能进行功能激活和聚集。血小板诱饵在体外抑制血小板在血栓形成表面的聚集和黏附，可通过添加正常血小板立即逆转；在兔模型中，血小板诱饵预处理可抑制动脉损伤诱导的血栓栓塞。诱饵还干扰血小板介导的人乳腺癌细胞聚集，并且它们的存在减少了微流控芯片上的人微血管中的癌细胞捕获和渗出。在转移的小鼠模型中，同时注射血小板诱饵和肿瘤细胞可抑制转移性肿瘤的生长。因此，我们的结果表明，血小板诱饵可能代表一种获得抗血栓和抗转移效果的有效策略。
