Key words :
Molecular "Mouse-trap" for Stem and Cancer Cells
8 Feb, 2008 06:09 pm
Six years ago, biomedical engineer Michael King was exploring the strange rolling motion of white blood cells when his research took a radical turn.
King shrugged and said, “I’ll give it a try.”
Six years later, King has pulled adult stem cells out of a living rat, using the cells’ peculiar rolling motion, with a far greater purity than any present technique. His research has also shown promise with cancer cells, exploiting the signaling process cells use to find infection, find a place to grow, or find a place to start a tumor.
One of the mysteries of the human immune system is the mechanics of how white blood cells, called neutrophils, flow so freely through the circulatory system but can leave the bloodstream and collect when and where they’re needed. When a foreign element invades the body, the interior of the wall of the nearby tiny blood vessels expresses an adhesive protein called selectin. The selectin binds very rapidly to a carbohydrate on the surface of a neutrophil and causes the cell to slowly roll along the vessel wall. The adhesion is perfectly balanced so the cell rarely sticks in one place or washes away with the blood flow. Instead, the cell rolls along like a stone on a riverbed. With its slower motion and constant contact with the vessel wall, the neutrophil can more easily look for a variety of chemicals and proteins called a chemokine that signal the cell to halt and crawl out of the vessel to the inflammation site.
Like neutrophils, cancer and stem cells respond to particular selectins. With the availability of stem cells Liesveld could provide, King began to explore the mechanics of exactly how these cells find their way to their destinations. In a new British Journal of Haematology paper, King and his colleagues at the University of Rochester show they can exploit the process by implanting a tube coated with human P-selectin protein into a living rat. The selectin coating remained active for 1-2 hours, and when King removed the device, he found he’d indeed captured cells straight out of the bloodstream, including contaminants—non-stem cells—as expected. What he didn’t expect was how many of the cells were viable stem cells.
“I was astounded,” says King. “More than 25 percent of the sample was stem cells. It’s amazing because even when you use drugs to increase the number of free stem cells in the blood, they still only make up less than 1 percent of all cells. If you use traditional methods to collect stem cells, centrifuging the rat’s blood, even in these drug-treated rats you might get 3 or 4 percent stem cells—meaning only 3 or 4 percent of the cells you obtain are stem cells.”
Centrifugal methods currently produce an overall higher stem cell yield than the selectin technique because they start with far more blood material, but King believes the microscale device can be scaled up to significantly larger capacity.
Beyond simply capturing cells, the exploitation of cellular rolling could lead to reprogramming cells that pass through such a device. As the cell rolls across the adhesive surface, it could be forced to contact other proteins on the surface. These proteins can be designed to steer a stem cell’s development, for instance, forcing it to become a specific type of blood, bone, or muscle cell.
King thinks someday an implantable device could continuously reprogram stem cells and neutrophils in the living bloodstream, but he is already hard at work on a device that holds the same promise for cancerous cells.
Since cancer cells use the same rolling mechanism to travel around the body and lodge in interstitial tissue, King and others are investigating which selectins cancer cells respond to. The researchers in his lab are working to create a microscale tube that might attract cancer cells and use “permanent” receptor-mediated triggering proteins to reprogram them to self-destruct. King has already verified that he can control the rolling adhesion of various types of cancer cells, including leukemias, prostate, retinoblastoma, and colorectal cancer cells.
“One of our ultimate goals is to develop an implantable device that will selectively remove metastatic cells from the blood,” says King. “Those cells can predate detectable tumors by years, so we might catch them before they become dangerous.”
Michael R. King et al. British Journal of Haematology, 3 March 2008.