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Human Vascular Microphysiological System for in vitro Drug Screening.

Publication ,  Journal Article
Fernandez, CE; Yen, RW; Perez, SM; Bedell, HW; Povsic, TJ; Reichert, WM; Truskey, GA
Published in: Sci Rep
February 18, 2016

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.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

February 18, 2016

Volume

6

Start / End Page

21579

Location

England

Related Subject Headings

  • Vasodilation
  • Vasoconstriction
  • Tumor Necrosis Factor-alpha
  • Tissue Engineering
  • Phenylephrine
  • Nitric Oxide
  • NG-Nitroarginine Methyl Ester
  • Lovastatin
  • Humans
  • Fibroblasts
 

Citation

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Fernandez, C. E., Yen, R. W., Perez, S. M., Bedell, H. W., Povsic, T. J., Reichert, W. M., & Truskey, G. A. (2016). Human Vascular Microphysiological System for in vitro Drug Screening. Sci Rep, 6, 21579. https://doi.org/10.1038/srep21579
Fernandez, C. E., R. W. Yen, S. M. Perez, H. W. Bedell, T. J. Povsic, W. M. Reichert, and G. A. Truskey. “Human Vascular Microphysiological System for in vitro Drug Screening.Sci Rep 6 (February 18, 2016): 21579. https://doi.org/10.1038/srep21579.
Fernandez CE, Yen RW, Perez SM, Bedell HW, Povsic TJ, Reichert WM, et al. Human Vascular Microphysiological System for in vitro Drug Screening. Sci Rep. 2016 Feb 18;6:21579.
Fernandez, C. E., et al. “Human Vascular Microphysiological System for in vitro Drug Screening.Sci Rep, vol. 6, Feb. 2016, p. 21579. Pubmed, doi:10.1038/srep21579.
Fernandez CE, Yen RW, Perez SM, Bedell HW, Povsic TJ, Reichert WM, Truskey GA. Human Vascular Microphysiological System for in vitro Drug Screening. Sci Rep. 2016 Feb 18;6:21579.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

February 18, 2016

Volume

6

Start / End Page

21579

Location

England

Related Subject Headings

  • Vasodilation
  • Vasoconstriction
  • Tumor Necrosis Factor-alpha
  • Tissue Engineering
  • Phenylephrine
  • Nitric Oxide
  • NG-Nitroarginine Methyl Ester
  • Lovastatin
  • Humans
  • Fibroblasts