Heterotypic Smooth Muscle Cell/Endothelial Cell Interactions Differ between Species

Background. In vitro coculture models have been used to study heterotypic cell-cell interactions. This study was performed to determine if species of cell origin affects heterotypic smooth muscle cell (SMC) endothelial cell (EC) interactions in coculture. Methods. To study the effect of ECs on SMC proliferation, ECs were cultured on porous Dacron membranes. SMCs were added opposite the ECs or on bare membranes on Day 3, and after 4 days, cells were harvested for cell counts. To study the effect of SMCs on EC proliferation, ECs at a density of 5 × 105 cells/membrane were added to bare membranes or on membranes opposite SMCs plated 2 days earlier. After 48 h, cells were harvested for cell counts. (N = 3/condition, experiments repeated ×2.) Cells of human and bovine aortic origin were used. Results. The effect of coculture on cell growth differed between species. The effect of heterotypic interactions between human cocultured cells was coinhibitory on the rate of growth as compared to the growth of cells cultured alone. Growth of cocultured ECs was 55.2 ± 8.7% less than that of ECs cultured alone while growth of cocultured SMCs was 27.2 ± 6.0% less than growth of SMCs cultured alone. This contrasted with the bovine EC stimulation of SMC proliferation, with 66.8 ± 5.0% greater growth of cocultured SMCs compared to SMCs cultured alone, and failure of bovine SMCs to decrease EC proliferation. Conclusions. Since significant differences in cell-material interactions occur in vivo between species, the finding that in vitro heterotypic cell-cell interactions are species dependent is not surprising. This fundamental difference in cell behavior stresses the potential importance of using human cells in studies evaluating cell-cell and cell-material interactions in vitro.