Marrow Stem Cell Differentiation for Valvulogenesis via Oscillatory Flow and Nicotine Agonists: Unusual Suspects?

Fluid-induced oscillatory shear stress (OSS) and nicotine are known antagonists in cardiovascular disease. However, from a regenerative medicine standpoint, we hypothesized that these parameters may support the cell differentiation of bone marrow mesenchymal stem cells (BMMSCs) for engineering heart valves. In this study, OSS and nicotine (10-6M) were applied individually to BMMSCs in monolayer culture. In both cases, a significantly higher expression of CD31 was detected compared to corresponding controls (p<0.05). We interpret our findings to indicate that both OSS and nicotine independently support mesenchymal to endothelial transformation; however, the underlying mechanism for this transformation in terms of the cell cytoskeletal structure was entirely different between the two stimulants. In the case of OSS, F-actin filaments exhibited a stretching response and formed a preferential alignment with each other. However, in the nicotine-treated group, a clear increase was observed in the number of actin filaments present, which led to the maximum expression of CD31 in comparison to the OSS and control groups. From our findings, we speculate that while nicotine may stimulate an increase in the differentiation of BMMSCs to endothelial cells, OSS may play a greater role in cellular distribution and the eventual creation of a tissue engineered heart valve (TEHV) endothelium.