Preparation of vascular endothelialized fiber shaped tissues for potential application in vascular toxicity testing by using cell self-aggregation technique

Abstract

An ideal vascular toxicity testing model would be the development of a vascular-like tissue constructs that can be used to evaluate changes over time in their structure at specific focal locations without shielding by gel adsorption of test drugs in extracellular matrix gels during induction of three dimensional vascular lumen formation. In this study, we have successfully prepared fiber-shaped cell aggregates composed of human umbilical vein endothelial cells and human mesenchymal stem cells as vascular pericytes anchored on the bottom of culture dishes at a defined location using our developed cell self-aggregation technique and a specific dumbbell-shaped culture chamber. The fiber-shaped cell aggregates maintained their shape for at least two weeks without rupture, and histological analysis interestingly revealed that they formed a unique tissue structure with multiple capillary-like structures oriented in the same direction as the long axis of the fiber in the medial side and a gapless monolayer of endothelial cells on the outer side, respectively. Then, it was shown that exposure of cadmium chloride to such vascular endothelialized fiber-shaped tissues elicited a toxic response in which only their outer endothelial layer disintegrated while maintaining their fiber shape. These results suggest that our vascular endothelialized fiber-shaped tissue could have the potential to be used as a model for vascular toxicity testing that enable us to evaluate toxicity over time without shielding by gel adsorption of test drugs, and we are continuing to analyze the results in detail.