01.23.08
The HemoShear 2.0
A new device invented by researchers at the University of Virginia could save pharmaceutical companies significant time and money in screening potential new drug compounds. Brett Blackman, an assistant professor in biomedical engineering and Brian Wamhoff, assistant professor in the department of medicine; cardiovascular division, teamed up to create a novel system, the HemoShear 2.0, which, for the first time, offers researchers the ability to observe the behavior patterns of human vascular cells under a variety of blood flow conditions that occur inside the body’s cardiovascular system.
Dr. Blackman said, “We want to help the pharmaceutical industry identify effective therapeutic compounds by allowing them to fail early, fail fast and fail cheap before going to very expensive animal studies.”
Atherosclerosis, hardening or narrowing of the arteries, is considered the most important underlying cause of heart attack or stroke. The HemoShear 2.0 models the early indicators of atherosclerosis by placing actual human endothelial cells, the cells lining the interior of blood vessels, and smooth muscle cells, the cells found in the wall of blood vessels, in an environment that mimics an artery with blood flowing through it. Data from these exposures are recorded and measured to help test the efficacy of therapeutic compounds and aid in early stage toxicity studies. Instead of testing drug compounds on isolated cells, which can produce false negatives, drug companies can use the device to test compounds in a more realistic environment.
This kind of modeling offers unique opportunities to observe the cells and their interaction. This interaction is important because the cells lining the interior of the blood vessels recognize different blood flow patterns imposed upon them and respond by expressing or repressing genes. This, in turn, influences their interactions with the cells found in the walls of blood vessels. The researchers found these cell interactions may lead to the onset of early-inflammation-associated atherosclerosis in certain arteries.
MRI’s were used by researchers to determine the rhythmic pattern that blood flows through different arteries in human subjects. Blackman said, “We are then able to simulate the same flow patterns in those areas that are more or less susceptible to atherosclerosis and observe how the cells respond to these flow patterns in HemoShear.”
Using a synthetic elastic layer that is similar to a real blood vessel wall, endothelial cells are plated on the top surface and smooth muscle cells on the bottom surface. Then, the different blood flow patterns modeled from human circulation are applied to the endothelial cells through rotation of a motor-driven cone system. The findings: the blood flow can influence both endothelial and smooth muscle cell behaviors.
When subjected to atheroprotective blood flow patterns, the endothelial cells aligned with the direction of the blood flow, and the smooth muscle cells aligned perpendicularly to the flow as is true in a healthy blood vessel. In stark contrast, the atheroprone type of flow caused the endothelial cells to move away from their parallel structure while smooth muscle cells moved away from their perpendicular structure.
This remodeling mimics the early phases of the diseased state of the artery; the blood flow pattern associated with atheroprone areas resulted in inflammation in both cells reminiscent of early hallmarks of atherosclerosis. This was confirmed through evaluating gene and protein expression profiles in both cell types.
Thomas Skalak, professor and chair of the U.Va. Department of Biomedical Engineering said, “the results of this study validate the use of this novel co-culture system as a relevant biomimetic vascular model for studying early atherosclerotic events. The cells’ responses to these carefully controlled models of blood flow can now be used to develop therapeutic interventions for detection and treatment of vascular diseases. It has the potential to be revolutionary.”
You’ve been listening to the Oscar Show, I’m Jacob Canon. Join us next week as we again delve into the election season, when our topic will be the work of Bryan Pfaffenberger, associate professor at the University of Virginia’s School of Engineering and Applied Science and his study of mechanical-lever voting machines, their history and understanding the interaction between technology and culture that has been going on for more than a century…