These platelet ‘decoys’ could prevent blood clots without spreading cancer
By Jennifer Couzin-Frankel
Like Jekyll and Hyde, the platelets in your blood are both good and evil. These specialized blood cells halt bleeding and help reconstruct injured tissue. But they can also cause dangerous blood clots and protect cancer cells as they travel from one site to another. Now, a team of bioengineers has taken the first step toward tipping this balance to the light side by creating “platelet decoys,” which in the lab mimic the real thing without causing clots.
“It’s a really fascinating sort of drug approach,” says Susan Smyth, chief of cardiology at the University of Kentucky in Lexington, who was not involved with the study.
Platelets are more harmful in some people than in others. Those at high risk of blood clots—such as someone who’s recently had a heart attack or a blood clot in their lung—are often put on antiplatelet drugs. But if people on these medications need surgery or get into a serious accident, they’re at high risk of bleeding. In patients with cancer, previous work has found that platelets bind to cancer cells and, by building something of a clot-wall around the cells, cushion them as they journey through the bloodstream and seed elsewhere in the body.
It was this dance between platelets and cancer cells that first attracted Anne-Laure Papa, a bioengineer at George Washington University in Washington, D.C. In 2014, she and her colleagues reported that inhibiting platelets before chemotherapy in animals reduced tumor growth. Papa then turned her attention to how platelets drive metastasis. “Can we design something that could interfere with” platelets’ protection of cancer cells, she wondered, making it harder for tumors to crop up elsewhere? She envisioned a “platelet decoy,” a structure that could compete with platelets in the bloodstream. Cancer cells could bind to the decoys, but they wouldn’t benefit from safe travel in the same way they do with real platelets.
At the time, Papa was working in the lab of cell biologist and bioengineer Donald Ingber, who directs the Wyss Institute at Harvard University in Boston. He suggested starting with a strategy he’d used in the past: Immersing cells in chemicals that strip away parts of their membrane and much of their contents. “You’re left with these little whiffle balls,” Ingber says. If the same was done to platelets, the stripped-down clot-stoppers could still bind to cells and “take up spaces where the normal platelets would go,” Ingber reasoned. But unlike real platelets, they wouldn’t cause clotting.
To test the idea, the researchers added their stripped-down platelets to healthy platelets in a petri dish. They impaired the platelets’ natural clotting mechanism. On a “lab on a chip” that mimics the kind of clotting that can cause heart attacks, the decoys also blocked clotting when mixed with real human platelets.
Next, the group tested its decoys in rabbits. The researchers used a suture to injure part of the animal’s carotid artery, causing blood clots to form there. The team then infused platelets, decoys, or a mixture. Adding decoys, even when combined with normal platelets, prevented blood clots from growing and migrating into the circulation. Studies in mice found that when they were injected at the same time as platelets and cancer cells, platelet decoys made with human cells could prevent the spread of breast cancer, the team reports today in Science Translational Medicine.
Smyth says one of the problems she and other cardiologists run into is that the body takes a week or more to clear some antiplatelet drugs. This means that patients needing surgery must stop taking medication about 5 to 10 days beforehand—putting them at risk of clots during that time. Papa’s and Ingber’s work suggests that unlike antiplatelet drugs, it’s easy to quickly eliminate the effect of decoys from the body by administering real platelets. This means the decoys may be useful in that 10-day period for patients who can’t be on the drugs because of impending surgery, but who are also at risk of blood clots without those drugs.
But what if the stripped-down platelets disappear too quickly? If their half-life is just a few minutes, their usefulness in patients will be limited, says Mortimer Poncz, a pediatric hematologist at Children’s Hospital of Philadelphia in Pennsylvania who is also working on strategies to combat the negative effects of platelets. Papa says how long the decoys endure, and whether they might be coaxed to circulate even longer than platelets, is something she plans to study.
Offering these decoys to patients is a long way off, but experts agree they could prove useful as a research tool more quickly. “There’s so much to learn,” says Jason Katz, a cardiologist and critical care physician at the University of North Carolina in Chapel Hill. Papa agrees, suggesting that biologists might use the decoys in experiments to untangle how platelets bind to different cells.
*Clarification, 13 February, 5:30 p.m.: This item has been updated to clarify how long it takes the body to clear antiplatelet drugs.
Source: sciencemag.org — Read: Original Article