Scott D. Cardone

Introduction. Cardiovascular disease (CVD) is the leading cause of death for both men and women in the United States. With 1 in 4 deaths resulting from CVD, the American Heart Association estimates its annual health care cost to be $316 billion.¹ Often, a patient will need a surgical operation to bypass an occluded coronary artery (coronary artery bypass graft, CABG). Presently, it is common to autotransplant the internal mammary artery or a small diameter vein from an extremity to perform the bypass. Certain circumstances, however, preclude this option.² One of the most provocative alternatives is a tissue engineered vascular graft (TEVG), which could be integrated seamlessly in both anatomical structure and physiological function. In this review, we will explore the unique approaches that researchers are taking to direct the differentiation of human stem cells through exposure to mechanical stimuli. Methods. Attempts to grow blood vessels center around emulating the biophysical niche that directs and maintains endothelial cells in vivo. Stem cells are seeded either onto a plate,³ tubular scaffold,^4,5 or membrane⁶ and then exposed to combinations of shear stress and hoop strain both in the presence⁶ and absence of chemical growth factors. Levels of previously identified markers of cell differentiation are then quantified using PCR,^3–8 flow cytometry,^4,7 or immunofluorescence.^3–5,7,8 Results. Researchers have observed increased expression of endothelial or smooth muscle cells markers at varying rates of shear stress and hoop strain.^3–8 Endothelial cells were also observed to change their orientation to align themselves^5,7 with the direction of shear stress and begin to form tubular structures³ which may indicate a propensity to neovascularize. Conclusions. Studies have found correlation between exposure of stem cells to mechanical stimuli and their subsequent differentiation toward endothelial and smooth muscle cells in the pursuit of engineering a blood vessel in vitro, which could one day be implanted for use in coronary artery bypass or other revascularization procedures. More research needs to be done to identify the ideal combination of mechanical stimuli that could become a recipe for engineering blood vessels.

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