Date(s) - 09/20/2017
Cardiovascular disease is the leading cause of death in the United States. Tissue engineered blood vessels (TEBVs) offer the potential to develop new treatments for vascular disease. TEBVs have been used clinically as vascular grafts, and may also serve as 3D human disease models to screen potential therapeutics. However, most vascular diseases are localized in nature, requiring TEBVs with spatially distinct disease regions. Research in the Rolle lab focuses on engineered cellular self-assembly to create functional, 3D tissue rings from cells and cell-derived extracellular matrix. The self-assembly system allows one-step 3D tissue ring fabrication by seeding a cell suspension into an agarose well. Agarose wells are molded from polydimethylsiloxane (PDMS) templates, which can be autoclaved and re-used. Cell rings self-assemble within 24 hours, are strong enough to harvest within 1-3 days after seeding, and the ring format is well suited for quantitative functional analysis of cell-derived tissues (e.g., uniaxial tensile testing, wire myography). Gelatin microspheres can be mixed and co-seeded with cells to achieve growth factor delivery within individual ring segments. In addition to vascular grafts, the system can be used to create other types tissue, including cartilage/tracheae. Recently, we demonstrated that self-assembled cell rings can serve as 3D tissue models of human vascular disease. Vascular tissue rings were generated by self-assembly of induced pluripotent stem cell (iPSC)-derived human vascular smooth muscle cells from healthy subjects or patients with supravalvular aortic stenosis (SVAS). Ongoing work focuses on creation of 3D vascular tissue tubes with focal regions of stenosis to model intimal hyperplasia.