Engineers use blood's hydrodynamics to manipulate stem, cancer cells

A tiny, implantable device has pulled adult stem cells out of a living rat with a far greater purity than any present technique. The test of the device designed by Michael R. King, associate professor of biomedical engineering at the University of Rochester, will be reported in the March 3 issue of the British Journal of Haematology.

“It’s the kind of research that, before we tried it, we never would have expected such a remarkable result straight out of the gate,” says King. “We’re finding we can play off the hydrodynamics of moving blood to isolate and manipulate specific cell populations with great efficiency.”

King is at the forefront of a new field; manipulating stem cells, white blood cells, and even cancer cells by exploiting the mechanics of the cells’ movement with such precision that he is having success capturing and even reprogramming several cell types as they pass through the device, he says.

A chance encounter between an engineer and a hematology clinician gave rise to the field in 2002.

King was studying how certain white blood cells, called neutrophils, know how to migrate to a point of infection. He observed how, near an injury site, the walls of the nearby blood vessels expressed an adhesive protein called a selectin, and if passing neutrophils brushed against these selectins, they stuck to the vessel wall.

But the cells did not remain stuck—they rolled. With a precise balance between the adhesion of the selectins and the forces of the flowing bloodstream, the cells could move much more slowly as they approached the infection site. With that slowed pace, the cell can look for a second signal on the vessel wall that tells the cell to exit the vessel by squeezing between cells in the wall and moving directly to the site of infection.

One reason the system is so effective is that only the neutrophils respond to those selectins, so only neutrophils slow down in the blood.

King was working out the physical dynamics of this neutrophil rolling in his office one day when Jane Liesveld, a hematology clinician doing work on bone marrow stem cells at the University of Rochester, walked by and noticed a poster of King’s work in the hallway outside his office.

“She dropped in and said, ‘I have a pretty plentiful source of primary stem cells from patients. Can you think of any biophysical research to do with that?’” says King. “The stem cell angle just fell from the sky.”

As King worked with Liesveld he found that the basic rolling mechanism was the foundation of a number of other processes, including stem cell transplantation—a natural phenomenon where stem cells move in and out of bone tissue via the blood. In 2004, he found that he could coat a material with specific adhesive selectins and capture living stem cells. This collaboration resulted in two human stem cell papers published just within the last month: in Biotechnology Progress (Charles et al., 2007) and Clinical Chemistry (Narasipura et al., 2007).

In the new British Journal of Haematology paper, King and colleagues show they can take the process a step further by implanting the device in a living rat with the selectin coating remaining active for 1-2 hours. When the tube was removed, King 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.”

King points out that centrifugal methods currently produce an overall higher stem cell yield because they start with far more blood material, but he believes his microscale device can be scaled up to significantly larger capacity.

King is even more enthusiastic about his work in reprogramming cells that pass through his device. As the cell rolls across the adhesive surface, it can be forced to contact other proteins on the surface. King says these proteins can be designed to steer a stem cell’s development, forcing it to become a specific type of blood, bone, or muscle cell.

King hopes someday an implantable device could continuously reprogram errant neutrophils, but he is already hard at work on a device that holds the same promise for cancerous cells.

Cancer cells use the same rolling mechanism to travel around the body and lodge in interstitial tissue, so King has already focused on isolating the selectins that cancer cells respond to. His lab is working to create a microscale tube that might attract cancer cells and use “permanent” receptor-mediated triggering proteins to reprogram them to self-destruct. With his microscale tube device, 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.”

Source: University of Rochester

Related stories:

MIT works toward novel therapeutic device
MIT and University of Rochester researchers report important advances toward a therapeutic device that has the potential to capture cells as they flow through the blood stream and treat them. Among other applications, such a device could zapp cancer cells spreading to other tissues, or signal stem cells to differentiate.
Stem cells may look malignant, not act it
Call it the cellular equivalent of big glasses, a funny nose and a fake mustache. Bone marrow stem cells attracted to the site of a cancerous growth frequently take on the outward appearance of the malignant cells around them, University of Florida researchers report in a paper to be published in the August issue of Stem Cells.
Cancer-killing invention also harvests stem cells
Associate Professor Michael King of the University of Rochester Biomedical Engineering Department has invented a device that filters the blood for cancer and stem cells. When he captures cancer cells, he kills them. When he captures stem cells, he harvests them for later use in tissue engineering, bone marrow transplants, and other applications that treat human disease and improve health.
New Device Provides a Major Boost to Adult Stem Cell Research
A single cell with the potential to repair damaged heart muscle tissue . . . regenerate injured bone . . . create new cartilage or skin . . . even reverse nerve damage. Human stem cells offer tremendous hope for the development of revolutionary medical treatments for these and a variety of other human health problems. Up until now, however, stem cell research has been slowed by ethical controversy - as well as by the rarity of the extraordinary cells themselves.
Statins have unexpected effect on pool of powerful brain cells
Cholesterol-lowering drugs known as statins have a profound effect on an elite group of cells important to brain health as we age, scientists at the University of Rochester Medical Center have found. The new findings shed light on a long-debated potential role for statins in the area of dementia.
Gene directs stem cells to build the heart
Researchers have shown that they can put mouse embryonic stem cells to work building the heart, potentially moving medical science a significant step closer to a new generation of heart disease treatments that use human stem cells.
Small protein may have big role in making more bone and less fat
A small protein may have a big role in helping you make more bone and less fat, researchers say. "The pathways are parallel, and the idea is if you can somehow disrupt the fat production pathway, you will get more bone," says Dr. Xingming Shi, bone biologist at the Medical College of Georgia Institute of Molecular Medicine and Genetics.
New technique produces genetically identical stem cells
Adult cells of mice created from genetically reprogrammed cells—so-called induced pluripotent stem (IPS) stem cells—can be triggered via drug to enter an embryonic-stem-cell-like state, without the need for further genetic alteration.

News discussion:

Medicine & Health news