264 publications from this institution
Abdominal aortic aneurysm (AAA) is a local, permanent, irreversible dilation of the infrarenal section of the aorta that risks rupture until treated. AAA is defined as an infrarenal diameter 1.5 times the normal diameter. Currently, surgeons intervene when the aneurysm reaches a maximum diameter of 50mm [1]. 200,000 new cases are diagnosed each year in the US, with 500,000 new cases diagnosed worldwide [2]. This results in 15,000 deaths each year from AAA rupture in the US alone [3], with 8,000 deaths per year in the UK [4]. Literature supports the theory that small aneurysms may be as likely to rupture as larger aneurysms [5–7], and therefore, the need for a more reliable predictor of AAA rupture may have clinical importance.
Cardiovascular disease remains the number one cause of death in the United States. Most current surgical procedures to alleviate this disease rely on the availability of suitable small diameter vascular grafts, which are constrained by several limitations. Tissue engineering brings new hope to this field, but still faces many challenges. This review focuses on the molecular aspects of the different components of vascular tissue engineering. The topics addressed include the cell type, extracellular matrix, and physical and biochemical stimulation with respect to their role in the development of a tissue engineered vascular graft.
One of the major failings in vascular tissue engineering is the limited capacity of autologous differentiated cells to reconstitute tissues. A logical solution is to use multipotent progenitor cells, which in vascular treatments have been underutilized. Although biochemical stimulation has been explored to differentiate bone marrow-derived progenitor cells (BMPCs) to smooth muscle cells (SMCs), the use of biomechanical forces in differentiation remains unexplored. The purpose of this work was to explore the effects of cyclic strain alone on BMPC morphology, proliferation, and differentiation. BMPCs were isolated from rat bone marrow and, after 7 days in culture, the cells grew in distinct multilayered colonies. BMPCs were stimulated with 10% strain at 1 Hz for 7 days. Observations showed that cyclic strain inhibited proliferation (p < 0.05) and caused alignment of the cells (p < 0.05) and of the F-actin cytoskeleton perpendicular to the direction of strain. In addition, cyclic strain resulted in expression by the cells of vascular smooth muscle alpha-actin and h1-calponin. This work demonstrates the potential of physiologic biomechanical stimulation in the differentiation of BMPCs to SMCs, and this could have important implications for vascular tissue engineering and other therapies in which cell sourcing is a major concern.
