Tissue-engineered blood vessels as promising tools for testing drug toxicity

Abstract

Drug-induced vascular injury (DIVI) is a serious problem in preclinical studies of vasoactive molecules and for survivors of pediatric cancers. DIVI is often observed in rodents and some larger animals, primarily with drugs affecting vascular tone, but not in humans; however, DIVI observed in animal studies often precludes a drug candidate from continuing along the development pipeline. Thus, there is great interest by the pharmaceutical industry to identify quantifiable human biomarkers of DIVI. Small-scale endothelialized tissue-engineered blood vessels using human cells represent a promising approach to screen drug candidates and develop alternatives to cancer therapeutics in vitro. We identify several technical challenges that remain to be addressed, including high-throughput systems to screen large numbers of candidates, identification of suitable cell sources and establishing and maintaining a differentiated state of the vessel wall cells. Adequately addressing these challenges should yield novel platforms to screen drugs and develop new therapeutics to treat cardiovascular disease.

Keywords:

• drug induced vascular injury
• drug toxicity
• endothelial dysfunction
• tissue engineered blood vessels
• vasoactivity

Declaration of interest

GA Truskey was supported by a NIH grant UH3TR000505 and the NIH Common Fund for the Microphysiological Systems Initiative. CE Fernandez was supported by an American Heart Association Pre-doctoral Fellowship 14PRE20500062. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.