Permeability across a novel microfluidic blood-tumor barrier model

Background: The lack of translatable in vitro blood-tumor barrier ( BTB) models creates challenges in the development of drugs to treat tumors of the CNS and our understanding of how the vascular changes at the BBB in the presence of a tumor. Methods: In this study, we characterize a novel microfluidic model of the BTB ( and BBB model as a reference) that incorporates flow and induces shear stress on endothelial cells. Cell lines utilized include human umbilical vein endothelial cells co-cultured with CTX-TNA2 rat astrocytes ( BBB) or Met-1 metastatic murine breast cancer cells ( BTB). Cells were capable of communicating across microfluidic compartments via a porous interface. We characterized the device by comparing permeability of three passive permeability markers and one marker subject to efflux. Results: The permeability of Sulforhodamine 101 was significantly ( p < 0.05) higher in the BTB model ( 13.1 +/- 1.3 x 10(-3), n = 4) than the BBB model ( 2.5 +/- 0.3 x 10(-3), n = 6). Similar permeability increases were observed in the BTB model for molecules ranging from 600 Da to 60 kDa. The function of P-gp was intact in both models and consistent with recent published in vivo data. Specifically, the rate of permeability of Rhodamine 123 across the BBB model ( 0.6 +/- 0.1 x 10(-3), n = 4), increased 14-fold in the presence of the P-gp inhibitor verapamil ( 14.7 +/- 7.5 x 10(-3), n = 3) and eightfold with the addition of Cyclosporine A ( 8.8 +/- 1.8 x 10(-3), n = 3). Similar values were noted in the BTB model. Conclusions: The dynamic microfluidic in vitro BTB model is a novel commercially available model that incorporates shear stress, and has permeability and efflux properties that are similar to in vivo data.