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The Combination of Tissue-Engineered Blood Vessel Constructs and Parallel Flow Chamber Provides a Potential Alternative to In Vivo Drug Testing Models

Njoroge, Wanjiku; Hernández Hernández, Andrea C.; Idris Musa, Faiza; Butler, Robert; Harper, Alan G. S.; Yang, Ying

The Combination of Tissue-Engineered Blood Vessel Constructs and Parallel Flow Chamber Provides a Potential Alternative to In Vivo Drug Testing Models Thumbnail


Authors

Wanjiku Njoroge

Andrea C. Hernández Hernández

Faiza Idris Musa

Robert Butler



Abstract

Cardiovascular disease is a major cause of death globally. This has led to significant efforts to develop new anti-thrombotic therapies or re-purpose existing drugs to treat cardiovascular diseases. Due to difficulties of obtaining healthy human blood vessel tissues to recreate in vivo conditions, pre-clinical testing of these drugs currently requires significant use of animal experimentation, however, the successful translation of drugs from animal tests to use in humans is poor. Developing humanised drug test models that better replicate the human vasculature will help to develop anti-thrombotic therapies more rapidly. Tissue-engineered human blood vessel (TEBV) models were fabricated with biomimetic matrix and cellular components. The pro- and anti-aggregatory properties of both intact and FeCl3-injured TEBVs were assessed under physiological flow conditions using a modified parallel-plate flow chamber. These were perfused with fluorescently labelled human platelets and endothelial progenitor cells (EPCs), and their responses were monitored in real-time using fluorescent imaging. An endothelium-free TEBV exhibited the capacity to trigger platelet activation and aggregation in a shear stress-dependent manner, similar to the responses observed in vivo. Ketamine is commonly used as an anaesthetic in current in vivo models, but this drug significantly inhibited platelet aggregation on the injured TEBV. Atorvastatin was also shown to enhance EPC attachment on the injured TEBV. The TEBV, when perfused with human blood or blood components under physiological conditions, provides a powerful alternative to current in vivo drug testing models to assess their effects on thrombus formation and EPC recruitment.

Citation

Njoroge, W., Hernández Hernández, A. C., Idris Musa, F., Butler, R., Harper, A. G. S., & Yang, Y. (2021). The Combination of Tissue-Engineered Blood Vessel Constructs and Parallel Flow Chamber Provides a Potential Alternative to In Vivo Drug Testing Models. Pharmaceutics, 13(3), Article 340. https://doi.org/10.3390/pharmaceutics13030340

Journal Article Type Article
Acceptance Date Feb 27, 2021
Online Publication Date Mar 5, 2021
Publication Date Mar 5, 2021
Journal Pharmaceutics
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 13
Issue 3
Article Number 340
DOI https://doi.org/10.3390/pharmaceutics13030340
Keywords atorvastatin, cardiovascular disease, endothelial progenitor cells, ketamine, platelets, test tissue models
Public URL https://keele-repository.worktribe.com/output/419646
Publisher URL http://doi.org/10.3390/pharmaceutics13030340

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