Age Effects on Vascular Smooth Muscle: An Engineered Tissue Approach

Abstract

Tissue engineering of blood vessels offers a potential new therapy for patients with vascular occlusive disease. In addition, tissue engineering technologies offer the opportunity to study the biology of vascular cells in a biomimetic, three-dimensional environment. A model for vascular tissue engineering was used to study the effects of vascular cell age on extracellular matrix (ECM) deposition, cellular mitosis, and protein synthesis under controlled conditions in vitro. Blood vessels were grown using a three-dimensional polyglycolic acid (PGA) mesh that was seeded with either infant or adult porcine vascular smooth muscle cells. Mechanical forces in the form of pulsatile radial distension were applied for the duration of the 7-week growth period. Overall, infant cells exhibited higher levels of cellular proliferation, ECM deposition, and remodeling activity than cells derived from adult animals. In addition, vessels cultured from infant cells had enhanced physical properties compared to vessels cultured from adult cells. The differentiation state of the smooth muscle cells in the infant and adult constructs was unchanged from the native state. However, the levels of immature pro-collagen, although undetectable in the vessels grown from adult cells, were similar in native vessels and in vessels grown with infant cells. These studies have important implications for the study of aging and vascular disease and remodeling, as well as for the field of tissue engineering.