New way finds better drugs for heart disease
Co-Culture model: Blue – collagen matrix; White Diamonds – smooth muscle; Green Circle – monocytes; White Boxes – endothelial cells
A team of scientists at the University of Nebraska Medical Center invented a milestone between the petri dish and animal tests, which could save the drug development industry untold millions in research and development. Using a known technique called co-culture, the scientists invented a highly efficient way to create artificial arteries that could reduce the cost of drug discovery.
In the complex and expensive realm of drug discovery, scientists screen drugs in a series of increasingly expensive experiments. One of the earliest jumps in expense is going from testing drugs on cells in a petri dish to testing the drugs in living animals. Frequently, drugs that work in the petri dish eventually fail in animals.
Immunofluorescence (IF) staining of biomarkers of cells — 3D image of the co-culture system. Red: VE-cadherin (endothelium); Green: α-SMA (smooth muscle); blue: nuclei (smooth muscle).
But now, UNMC’s inventors can create a simulated artery that models the progression of coronary artery disease. The model can test new drugs that slow or reverse the progression of the leading cause of death in the United States, coronary artery disease.
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Gap junction between the endothelial cells (arrow heads) were identified under scanning electron microscope. Monocytes bond to endothelial cells at gap junction area (white arrows). Monocyte migrated into and underneath the endothelial cell layer (red arrow).
US provisional 62/490,133
To create the co-culture model, the inventors mixed human smooth muscle cells with isolated type I collagen. Afterwards, the inventors polymerized the collagen in an incubator for 20 minutes. When polymerized, the inventors plated endothelial cells on top of the polymerized collagen matrix and incubated the culture for 24 hours. After incubation, smooth muscle cells spread out through the collagen. The resultant culture contained a collagen gel impregnated with smooth muscle cells and a surface coated with a layer of endothelial cells.
The composite co-culture cells functioned as they would in a living artery. After creation, the cellular distribution stayed consistent with that of a living artery. In addition, biomarker expression from the cells in the culture was consistent with cells distributed in living tissue.
To accurately model atherosclerotic disease, the co-culture model will LDL have to model the accumulation of LDL cholesterol in the vasculature. The inventors introduced, fluorescently labelled LDL to the culture medium. After 24 hours, the inventors found labeled LDL distributed throughout the collagen scaffold.