Towards a Biohybrid Lung Assist Device: N-Acetylcysteine Reduces Oxygen Toxicity and Changes Endothelial Cells' Morphology.

Abstract

The development of an endothelialized membrane oxygenator requires solution strategies combining the knowledge of oxygenators with endothelial cells' biology. Since it is well known that exposing cells towards pure oxygen causes oxidative stress, this aspect has to be taken into account in the development of a biohybrid oxygenator system. N-Acetylcysteine (NAC) is known for its antioxidant properties in cells. We tested its applicability for the development of an endothelialized oxygenator model. Cultivating human umbilical vein derived endothelial cells (HUVEC) up to 6days with increasing concentrations of NAC from 1 to 30mM revealed NAC toxicity at concentrations from 20mM. Cell density clearly decreased after radical oxygen species exposure in non-NAC pretreated cells compared to 20mM NAC precultured HUVEC after 3 and 6days. Also the survival rate after ROS treatment could be restored by incubation with NAC from 15 to 25mM for all time points. NAC treated cells changed their morphology from typical endothelial cells' cobblestone pattern to a fusiform, elongated configuration. Transformed cells were still positive for typical endothelial cell markers. Our present results show the potential of NAC for the protection of an endothelial cell layer in an endothelialized membrane oxygenator due to its antioxidative properties. Moreover, NAC induces a morphological change in HUVEC similar to dynamic cultivation procedures.