When the platelets that help form blood clots become overactive, it can lead to heart disease and stroke, while also promoting the spread of malignant cancer cells. Antiplatelet drugs such as aspirin and Plavix (clopidogrel) have been developed to reduce dangerous blood clots. But reversing the effects of those drugs can take as long as a week, exposing patients to extra risk of uncontrolled bleeding in emergency situations.
Scientists at the Wyss Institute at Harvard University have created “decoy” platelets that they say can reduce blood clots and are also easily reversible. What's more, they may be able to be used to prevent cancer from spreading, they believe.
The team created the therapy by taking normal platelets and removing their outer lipid membrane and some inner contents. When these cells were added to normal human blood in a blood-vessel-like channel, the researchers observed reduced aggregation and binding. Similar results were also achieved in a rabbit model of vascular thrombosis. The researchers described the decoys in Science Translational Medicine.
“The decoys, unlike normal intact platelets, are unable to bind to the vessel wall and likely hinder the normal platelets’ ability to bind as well,” said the study’s first author, Anne-Laure Papa, Ph.D., in a statement.
The Wyss team also wanted to test their decoys in cancer, because platelets are known to shield cancer cells from the body’s immune system, thereby helping them spread to distant sites. In fact, scientists at the Medical University of South Carolina had previously found that platelets secrete a molecule called TGF-beta to suppress T-cell function. They showed that adding antiplatelet drugs to T-cell therapy inhibited melanoma growth in mice.
For the Wyss study, Papa and colleagues mixed decoys and normal platelets with human breast cancer cells and observed them in a model of the human vascular system. The decoys almost completely prevented the platelets from helping the cancer cells invade the channel wall. Mice given the concoction also saw significantly smaller and fewer metastatic tumors compared with those receiving normal platelets alone, the team reported.
More importantly, the scientists were able to rapidly reverse the decoys’ inhibition of normal platelet activity simply by transfusing functional platelets to the channels. If that can be translated in humans, patients could be prepared for surgery quickly, the researchers figure. And because the decoys can be created with the patient’s own platelets, they would not trigger a dangerous immune reaction.
“The reversibility and immediate onset of action are major advantages of our platelet decoys, and we envision them to be useful in hospital-based situations such as preventing clotting in high-risk patients just before they undergo surgery, or when given alongside chemotherapy to prevent existing tumors from spreading,” said Papa.
Before the cell therapy can be tested in humans, Papa and colleagues will need to improve the decoys so that they can stay in the bloodstream longer. They also plan to investigate the potential of the decoys to be used as carriers to help deliver drugs to tumor cells, which they argue could be the first step toward targeted prevention of metastatic cancer.