Wednesday, February 13, 2008

Plucking Cells out of the Bloodstream

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

By Katherine Bourzac

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

Multimedia •  Watch Michael King's new device in action.

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.

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.

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.