Evaluation of Arteriolar Smooth Muscle Cell Function in an Ex Vivo Microvascular Network Model

An emerging challenge in tissue engineering biomimetic models is recapitulating the physiological complexity associated with real tissues. Recently, our laboratory introduced the rat mesentery culture model as an ex vivo experimental platform for investigating the multi-cellular dynamics involved in angiogenesis within an intact microvascular network using time-lapse imaging. A critical question remains whether the vessels maintain their functionality. The objective of this study was to determine whether vascular smooth muscle cells in cultured microvascular networks maintain the ability to constrict. Adult rat mesenteric tissues were harvested and cultured for three days in either MEM or MEM plus 10% serum. On Day 0 and Day 3 live microvascular networks were visualized with FITC conjugated BSI-lectin labeling and arteriole diameters were compared before and five minutes after topical exposure to vasoconstrictors (50 mM KCl and 20 nM Endothelin-1). Arterioles displayed a vasoconstriction response to KCl and endothelin for each experimental group. However, the Day 3 serum cultured networks were angiogenic, characterized by increased vessel density, and displayed a decreased vasoconstriction response compared to Day 0 networks. The results support the physiological relevance of the rat mesentery culture model as a biomimetic tool for investigating microvascular growth and function ex vivo.