ADVANCE Fellows Award: The Development of a Tissue-Engineered Vascular Graft from Multipotent Adult Progenitor Cells

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0137590 Suggs Cardiovascular tissue engineering (CVTE) is an emerging field with the goal of creating vascular tissues that restore, maintain, or improve function based on the principles of engineering and the biologic sciences. The primary goal of this project is to develop a tissue-engineered vascular graft. Based on the current state of knowledge in the field of CVTE, several objectives can be outlined in the development of an ideal tissue-engineered vascular graft. The graft should have sufficient strength to be easily sutured and withstand arterial pressures. The cells used in developing the tissue-engineered construct, particularly endothelial cells, should be autologous and should be derived from adult individuals with minimal donor site morbidity.The PI plans to utilize techniques to drive multipotent cells towards smooth muscle cell and endothelial cell lineages. Once these cells have been differentiated using various soluble chemical factors, they will be seeded sequentially onto porous collagen foams and cultured under both pulsatile and shear stresses. The cell/collagen constructs will be evaluated relative to static controls with the hypothesis that the differentiated phenotype of the cells comprising the graft and the strength of the graft itself can be controlled and maintained by a combination of both chemical and mechanical stimulation.Coronary artery disease can be treated with various interventional procedures; however, these procedures have a high failure rate due to restenosis and often must be followed by surgical reconstruction. Conduits are typically removed from the same individual and used as a bypass around the affected artery. Some individuals have unsuitable arteries or veins because of varicosities, branching, or inadequate lumen size. If these autologous conduits are not available or not in satisfactory condition, there are no currently available grafts to replace the small diameter (4mm) coronary arteries. The development of an autologous conduit engineered from bone marrow cells would save the lives of patients who have no other options.