Endothelial cell migration in human plasma is enhanced by a narrow range of added sphingosine 1-phosphate:...

Sphingosine 1-phosphate (S1P) promotes endothelial cell migration in vitro and may potentially impact the endothelialization of implanted biomaterials. However, the effects of S1P on endothelial cells (EC) in flowing blood could be negligible due to preactivation of signaling cascades. We previously developed biomaterials that release S1P and wished to determine through in vitro experiments the extent to which EC respond to S1P added to human platelet poor plasma. We found that addition of 200 nM S1P to platelet poor plasma significantly increased cell migration in two migration models. A lower concentration of S1P added to plasma (100 nM) did not increase endothelial cell migration rates, while the cell migration response was saturated above 200 nM S1P. Expression of the main S1P receptor in EC, S1P(1), was elevated in plasma compared to low serum medium, but addition of VEGF or fluid flow elicited a further increase in S1P(1) mRNA, consistent with the synergistic effects observed between S1P, VEGF, and fluid flow. Thus, sustained delivery of S1P from biomaterials might only enhance endothelial cell migration if the concentration of S1P at the surface of the material stimulated adjacent EC to the same extent as approximately 200 nM S1P added to plasma.