The leading cause of death in the United States is coronary heart disease, which
is characterized by the narrowing of blood vessels that deliver blood and oxygen
to the heart. A possible way to treat this condition is to bypass the blocked
arteries, using an artery or vein taken from elsewhere in the patient’s body to go
around the blocked region. However, many candidates for these surgeries lack
adequate blood vessels that can be used for such purposes. For this reason, it is
important to develop a tissue engineered vascular graft (TEVG) that can be used
in place of a native vessel. In the Tranquillo Lab, the method for creating TEVGs
involves a cell-seeded fibrin gel that is remodeled over time. Initial animal studies
have shown that TEVGs created in this way contain proteins that promote clotting.
In native vessels, the surface exposed to blood flow is covered by a monolayer of
endothelial cells, which prevent clotting. Endothelial cells are also highly
immunogenic, so TEVGs created using endothelial cells would have to be made
using each patient’s own cells. In this study, we propose to use a monolayer of
mesenchymal stem cells (MSCs), which are non-immunogenic, on this surface
instead. We have shown that, when exposed to shear stress, MSCs exhibit decreased levels of platelet adhesion. Staining for endothelial cell markers suggests that we may be able to differentiate MSCs to a functional endothelial cell phenotype. If MSCs can be used as an alternative to endothelial cells in TEVGs, this therapy can potentially be available “off-the-shelf” to a large number of patients in the future.