Scientists from Nanyang Technological University in Singapore have developed a small, organ-on-a-chip device that is especially good for modeling atherosclerosis – the constriction of blood vessels that is the leading cause of heart attacks and strokes. The device could potentially help better understand patients atherosclerosis and develop new treatments.
In a paper appearing this week in APL Bioengineering, researchers illustrate how the new device could be used to study important inflammatory responses in cells that the vessel in ways that could not be done in animal models. The research team also explains how this organ-on-a-chip could improve blood testing for patients.
"Atherosclerosis is a very important and complex disease," said Han Wei Hou, a biomedical engineer at Nanyang Technological University in Singapore. It develops when fat, and other substances in the blood form that accumulates on the inside walls of arteries. This buildup constricts the blood vessel, causing cardiovascular diseases .
To address blood flow, the built-in device that fits on a single square-inch chip, consisting of two stacked chambers separated by a thin and flexible polymer membrane. The bottom contains air while the top contains a flowing fluid similar in mechanical properties to blood.
Inside the fluid-filled chamber on top of the membrane, the cells grow endothelial cells – the cells that line the inside of blood vessels. The researchers pump air into the bottom chamber, so the membrane stretches like a balloon and forms a bubble that blocks the flow. This process simulates the narrowing of a vessel.
The fluid-filled chamber constricts, causing the fluid to flow faster in some regions and slower in others. When the patients grew the cells under continuous but slow flow, endothelial cells were able to grow and express a protein called ICAM-1 ; this protein is associated with inflammation and is important in the development of atherosclerosis.
The researchers found that they replaced the cell culture media with human blood, more immune cells called monocytes bound to the endothelial cells in low-flow regions. Monocytes are mainly responsible for the accumulation of lipids, which eventually develop into the plaque that causes atherosclerosis.
These results are consistent with the accepted disease of the disease: Disturbed blood flow in constricted vessels promotes vascular inflammation , which encourages the recruitment of monocytes to help create plaques.
"[The device] has a lot of promise in terms of diagnostics," Hou said. As a proof-of-concept experiment, the pumped blood spiked with TNF-alpha , a protein that's a sign of inflammation, into their device. The inflamed blood caused more immune cells to bind to the endothelial cells than normal.
Measuring the number of immune systems in the blood, an indicator of early atherosclerosis . In contrast to other tests that just count the number of immune cells circulating in blood, this technique could more accurately assess early immune responses in patients.