Functional evaluation of circulating endothelial progenitor cells for vascular tissue engineering

One critical barrier to the success of vascular tissue engineering strategies is the need for appropriate endothelial cell sources. Adult stem and progenitor cells have emerged as a potentially promising cell source but very little is known about their functional potential. The endothelial cell (EC) resides on the vascular wall at the interface with flowing blood and is a key mediator of hemostasis and thrombosis. These studies investigated the use of endothelial progenitor cells (EPCs) derived from peripheral blood as a vascular lining on an engineered blood vessel substitute. Models were developed to investigate two aspects of the vascular environment, shear stress and substrate on EPC response at the gene, protein and functional levels. Isolation of EPC colonies from peripheral blood gave rise to cells which displayed an endothelial-like phenotype with expression of many EC specific markers and functions. Through the use of transcriptional profiling, results demonstrated that EPC gene expression was generally less sensitive to shear stress than ECs but shear stress preconditioning did result in upregulation of the EPC antioxidant defense system and promoted anticoagulant function. When co-cultured on a model of the vascular wall, EPCs altered their gene expression and favored a response more similar to mature vascular ECs. In a baboon arteriovenous shunt, shear stress preconditioned EPCs were able to resist platelet deposition and provided a non-thrombogenic lining on an engineered blood vessel substitute. Although significantly more research needs to be done, this work has provided an understanding of EPC function in the shear stress environment and provides evidence that EPCs are a viable endothelial cell source for vascular tissue engineering.Ph.D.Committee Chair: Nerem, Robert; Committee Member: Eskin, Suzanne; Committee Member: Gibbons, Gary; Committee Member: Hanson, Stephen; Committee Member: Vito, Raymon