Ingenieros usan la hidrodinámica de la sangre para manipular células madre del cáncerContributed by: Anonymous · Views: 1,721
Contributed by: Anonymous · January 25, 2008 @ 08:14 PM MST · Views: 1,721
Engineers Use Blood's Hydrodynamics to Manipulate Stem, Cancer Cells
Biomedical Engineers Design an Implantable Cell Retriever and Reprogrammer
Movie: How stem cells are made to roll inside device
Movie: Rushing blood rolls stem cells along wall of device
Movie: Neutrophils' natural rolling inside a living capillary
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).
Cells sticking to micropatterned selectin molecule
"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.
Michael King, associate professor of biomedical engineering (credit: Richard Baker, University of Rochester)
"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."
This research was funded by the New York State Foundation for Science, Technology and Innovation, and by CellTraffix, a company in which King holds a financial interest. Other authors on the British Journal of Haematology paper include University of Rochester postdoctoral students Joel C. Wojciechowski and Srinivas D. Narasipura, doctoral student Nichola Charles, Deanne Mickelsen, laboratory technician, and Martha L. Blair, professor in the Department of Pharmacology and Physiology.
Contact: Jonathan Sherwood email@example.com 585.273.4726
Courtesy: University of Rochester, News Home Page