Human Vascular Microphysiological System for in vitro Drug Screening.
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In vitro human tissue engineered human blood vessels (TEBV) that exhibit vasoactivity can be used to test human toxicity of pharmaceutical drug candidates prior to pre-clinical animal studies. TEBVs with 400-800 μM diameters were made by embedding human neonatal dermal fibroblasts or human bone marrow-derived mesenchymal stem cells in dense collagen gel. TEBVs were mechanically strong enough to allow endothelialization and perfusion at physiological shear stresses within 3 hours after fabrication. After 1 week of perfusion, TEBVs exhibited endothelial release of nitric oxide, phenylephrine-induced vasoconstriction, and acetylcholine-induced vasodilation, all of which were maintained up to 5 weeks in culture. Vasodilation was blocked with the addition of the nitric oxide synthase inhibitor L-N(G)-Nitroarginine methyl ester (L-NAME). TEBVs elicited reversible activation to acute inflammatory stimulation by TNF-α which had a transient effect upon acetylcholine-induced relaxation, and exhibited dose-dependent vasodilation in response to caffeine and theophylline. Treatment of TEBVs with 1 μM lovastatin for three days prior to addition of Tumor necrosis factor - α (TNF-α) blocked the injury response and maintained vasodilation. These results indicate the potential to develop a rapidly-producible, endothelialized TEBV for microphysiological systems capable of producing physiological responses to both pharmaceutical and immunological stimuli.
Published Version (Please cite this version)10.1038/srep21579
Publication InfoBedell, HW; Fernandez, CE; Perez, SM; Povsic, Thomas Joseph; Reichert, WM; Truskey, George A; & Yen, RW (2016). Human Vascular Microphysiological System for in vitro Drug Screening. Sci Rep, 6. pp. 21579. 10.1038/srep21579. Retrieved from http://hdl.handle.net/10161/11943.
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Associate Professor of Medicine
R. Eugene and Susie E. Goodson Professor of Biomedical Engineering
My research interests focus upon the effect of physical forces on the function of vascular cells and skeletal muscle, cell adhesion, and the design of engineered tissues. Current research projects examine the effect of endothelial cell senescence upon permeability to macromolecules and the response to fluid shear stress, the development of microphysiological blood vessels and muscles for evaluation of drug toxicity and the design of engineered endothelialized blood vessels and skelet
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