A Morphological Study on Migration and Proliferation of Smooth Muscle Cells by Endothelial Cells in Full Layer Vascular Wall Model

ABSTRACT

To study the biology of the endothelium and the media of the vascular wall, full layer vascular wall model was constructed in vitro. In the experimental vascular wall model, endothelial cell (EC)s were grown on a collagen lattice containing multilayers of smooth muscle cell (SMC)s and a EC-free portion was made by a cloning ring on the culture disc. As conditioned culture media of ECs-SMCs contain biologic mediators that may promote the growth of SMCs, the availability of this vascular wall model promptly us to examine the extent to which ECs regulate the migration and proliferation of SMCs when these cells are maintained with or without covering EC lining in coculture. Morphologic characteristics of full layer vascular wall model was a whitish, non-transparent membrane. Outer boundaries and the zone of no EC were thicker than that of central portion. By light microscope imaging, luminal surface was composed of EC monolayer, and SMCs and collagen fibers were distributed between the polyethylene terephtalate (PET) membrane and EC monolayer. SMCs and collagen fibers were mainly located near the PET membrane. Venous SMCs were densely infiltrated as compared to arterial SMCs. By scanning electron microscopy, EC monolayer and dense collagen fibers in the zone of no EC were clearly shown. On the effects of platelet derived growth factor (PDGF) in the proliferation of SMCs and modeling of full layer vascular wall model, no effect on SMC in the zone of EC covering was seen however, active migration and proliferation of SMCs were noted in the zone of no EC. Wall thickness was two times greater than that of control. On the effects of EGF, it was observed that EGF markedly stimulated migration of SMCs with or without EC coverings in contrast to the control group. On the effects of FGF, results were similar to the PDGF group. Results on the effect of IGF-1 were similar to the PDGF group. As conclusions, full layer vascular wall model in this study was proved to be a good laboratory model for basic vascular research. And SMCs migration and proliferation were more active in venous SMCs compared to arterial SMCs. The collagen fibers were also richer and the wall was more thickened. EGF was most the potent SMC stimulator. PDGF, FGF, and IGF-1 were moderate SMC stimulator in the zone of no EC covering. These results strongly support why intimal hyperplasia eventually occured in autogenous venous bypass graft.