Towards a Biohybrid Lung Assist Device: N-Acetylcysteine Reduces Oxygen Toxicity and Changes Endothelial Cells’ Morphology
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 6 days with increasing concentrations of NAC from 1 to 30 mM revealed NAC toxicity at concentrations from 20 mM. Cell density clearly decreased after radical oxygen species exposure in non-NAC pretreated cells compared to 20 mM NAC precultured HUVEC after 3 and 6 days. Also the survival rate after ROS treatment could be restored by incubation with NAC from 15 to 25 mM 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.
KeywordsTissue engineering Extracorporeal membrane oxygenation ECMO Extracorporeal carbon dioxide removal ECCO2R Oxygenator
We thank Ting-Yi Yang for technical assistance.
Conflict of interest
Dr. Cornelissen is grant holder of the IZKF Project Number T12 that made this research possible. Mr. Plein, Dr. Thiebes, Dr. Finocchiaro, Mr. Hesselmann, Prof. Steinseifer and Prof. Jockenhoevel declare that they do not have any conflict of interest.
Supported by a Grant from the Interdisciplinary Center for Clinical Research within the faculty of Medicine at the RWTH Aachen University (IZKF Project Number T12).
Institutional review was obtained for the use of donated human umbilical cords (vote of the local ethics committee: EK 019/16). No further studies involving human subjects were carried out. The research did not involve animal studies.
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