Potential of Tissue Engineered Blood Vessel as Model to Study Effect of Flow and Wall Thickness on Cellular Communication

In physiology, blood vessel function is maintained mainly through nitric oxide (NO)-mediated cross-talk between endothelial cells (ECs) and smooth muscle cells (SMCs), which is compromised in pathology. Lack of an appropriate in vitro model hampers the study of vascular disease progression mechanisms. This study attempted to use tissue engineered blood vessel (TEBV) as a model system to understand the effect of wall thickness and shear stress on EC to SMC communication. Differentiated ECs and SMCs obtained by in vitro culture of sheep peripheral blood mononuclear cells (PBMNCs) were seeded on biodegradable €-polycaprolactone (PCL) conduits of different wall thicknesses and exposed to shear stress in a two-channel bioreactor to construct functional TEBV. Phenotypes of ECs and SMCs were studied in terms of nitric oxide synthase (eNOS) and basic calponin expressions respectively, using real time polymerase chain reaction. Endothelial to SMC cross-talk under the influence of wall thickness and shear stress was interrelated to NO and cyclic GMP (cGMP) production. Shear stress accelerates, but wall thickness has no influence on endothelial NO production. Increased release of NO in response to shear stress resulted in augmented cGMP production, but only when the wall thickness was lower. Both wall thickness and shear stress affect cGMP production and smooth muscle contractile phenotype. From this study, it is also suggested that TEBV may be a suitable model to study various risk factors on vessel integrity.