Vincristine

To demonstrate the application of the vascularized MPS for studies of drug effects, microfluidic devices and 2D cell cultures of endothelial and tumor cells were exposed to three test compounds. FDA-approved anti-cancer drugs Fluorouracil (5-FU, S1209; concentrations tested: 1, 10, 100, 300, 1000 μM), Vincristine (S1241; concentrations tested: 1, 10, 100, 300, 1000 nM), and Sorafenib (S7397; concentrations tested: 0.1, 1, 10, 30, 100 μM), were purchased from Selleckchem (Houston, TX). All test compounds were dissolved in 100% cell culture grade dimethyl sulfate (DMSO, Fisher Scientific) to 200 mM for 5-FU and Vincristine and 20 mM for Sorafenib (i.e., 200× of the top test concentration). Final concentration of DMSO vehicle was 0.5% v/v in all conditions. Drug or vehicle treatments were introduced to the microfluidic devices through cell culture medium channels and reservoirs on day 6 post-loading. The interstitial flow was maintained by transferring cell culture medium from the outlet reservoir to the inlet reservoir daily to re-establish the interstitial pressure. Cell culture medium with drugs and/or vehicle was replaced with fresh EGM-2 on day 8 and the devices were monitored for another 2 days until day 10.