In-vitro smooth muscle-endothelial cell coculture to characterize cardiovascular therapeutics
Abstract
Stent-related cardiovascular therapeutics has become a major research avenue due to the size and growth rate of the affected population. Effective and versatile in vitro models allow for a greatly reduced cost as therapeutics are perfected, focusing on denudation of the inner endothelial cell (EC) layer during balloon angioplasty and uncontrolled proliferation of smooth muscle cells (SMC). Our lab has previously established that direct contact interactions between EC and SMC in vitro layers are important when describing cellular response mechanisms. EC seeding density, soluble media factors, and SMC differentiation pretreatments can be used to modulate between healthy and hyperplastic states. An in vitro smooth muscle-endothelial cell coculture model of healthy and diseased arteries has been established and optimized to further enable high-throughput characterization of cardiovascular treatments. We also evaluated a novel cardiovascular therapeutic, DS-SILY20, on these in vitro cocultures and examined smooth muscle cell differentiation and pro-inflammatory cytokine expression. Direct contact of smooth muscle cells and endothelial cells has the greatest effect on smooth muscle cell differentiation. DS-SILY20 seems to have a greater therapeutic effect on the endothelial cell layer, and reduces expression of interferon gamma and tumor necrosis factor-alpha. We also found that these direct-contact cocultures provide a significantly different result under DS-SILY20 treatments, when compared to the standard monoculture platforms.
Degree
M.S.B.M.E.
Advisors
Panitch, Purdue University.
Subject Area
Biomedical engineering
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