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Biomedicine

Plucking Cells out of the Bloodstream

A new implantable device can extract stem cells for therapeutic transplant or program cancer cells to die.

Bioengineers have developed an implantable device that captures very pure samples of stem cells circulating in the blood. The device, a length of plastic tubing coated with proteins, could lead to better bone-marrow transplants and stem-cell therapies, and it also shows promise as a way to capture and reprogram cancer cells roaming the bloodstream. The company CellTraffix is commercializing the technology.

Cell catcher: University of Rochester bioengineer Michael King holds up a section of plastic microtubing lined with proteins that trap cancer and stem cells.

When patients get bone-marrow transplants, what they’re really receiving are infusions of a type of adult stem cell. Bone-marrow-derived stem cells play a crucial role in renewing the blood throughout adulthood, creating new cells to carry oxygen and fight infections. These adult stem cells can be sampled using the new device.

The new device mimics a small blood vessel: it’s a plastic tube a few hundred micrometers in diameter that’s coated with proteins called selectins. The purpose of selectins in the body seems to be to slow down a few types of cells so that they can receive other chemical signals. A white blood cell, for instance, might be instructed to leave the circulation and enter a wound, where it would protect against infection. “Selectins cause [some] cells to stick and slow down,” says Michael King, a chemical engineer at the University of Rochester who’s developing the cell-capture devices. Different types of selectins associate with different kinds of cells, including platelets, bone-marrow-derived stem cells, and immune cells such as white cells.

In an upcoming publication in the British Journal of Hematology, King reports that selectin-coated microtubes implanted in rats can capture very pure samples of active stem cells from circulating blood. He gave a similar demonstration of stem-cell purification with samples taken from human bone marrow last year. Cancer patients often require bone-marrow transplants following harsh chemotherapy and radiation treatments that kill adult stem cells in the blood.

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The purity of these transplants can be a matter of life or death. When the transplant is derived from the patient’s own bone marrow–extracted before treatment–it’s critical that it not contain any cancer cells. When it comes from another person, there’s a chance that the donor’s immune cells will attack the recipient if they’re not filtered out. But current purification methods are slow and inefficient, King says. Those that rely on antibody recognition or cell size and shape typically extract only a small fraction of the stem cells in a blood sample; the rest go to waste.

Twenty-eight percent of the cells captured by King’s implants were stem cells. “This is astounding given how rare they are in the bloodstream,” says King. Implants would probably not be able to capture enough stem cells for transplant. But King believes that filtering a donor’s blood through a long stretch of selectin-coated tubing outside the body, in a process similar to dialysis, would be very efficient. “This technique will clearly be useful outside the body” as a means of purifying bone-marrow-derived stem cells, says Daniel Hammer, chair of bioengineering at the University of Pennsylvania.

Hammer believes that King’s devices will also have broader applications as implants that serve to mobilize a person’s own stem cells to regenerate damaged tissues. By slowing down cells with selectins and then exposing them to other kinds of signals, says Hammer, King’s devices “could capture stem cells, concentrate them, and differentiate them, without ever having to take the cells out of the body.” There might be a way to use selectins to extract neural stem cells, too.

“This is a very broad-reaching discovery,” says Hammer. Indeed, King says that he has already had some success using selectin coatings to reprogram cancer cells.

Cancer cells appear to highjack selectin pathways in order to spread to other parts of the body, the process known as metastasis. Tumors shed cells into the bloodstream. Some of those cells seem to exit with the help of selectins; ensconced in new tissue, they then establish new tumors. These secondary tumors cause more cancer deaths than initial tumors do.

King says he has unpublished work demonstrating that leukemia cells that roll along a coating of selectins and a cancer-specific signaling molecule will go through a process called programmed cell death. Healthy stem cells also roll across the device because they’re attracted to the selectins, but the death signal doesn’t affect them. Leukemia is a blood cancer, but King expects that the anticancer coating would work for solid tumors as well. Devices lined with these coatings might be implanted into cancer patients to prevent or slow metastasis.

King hopes to test antimetastasis implants in animals this year. He’s collaborating with Jeffrey Karp, a bioengineer at the Harvard-MIT Division of Health Sciences and Technology, and Robert Langer, an MIT Institute Professor, to develop selectin coatings that are stable over months rather than days.

CellTraffix CEO Tom Fitzgerald says that the company’s first product, a kit that will enable researchers to capture large numbers of stem and cancer cells in the lab, will likely reach the market early next year. The company hopes to begin clinical testing of the anticancer coatings by early 2010.

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