Endothelium-on-a-chip for permeability studies in diabetic and diabetic kidney disease milieu
Organ-on-a-chip (OOC) technology is a valuable tool that can facilitate a faithful replication of target tissues or organs by enabling the application of important physiological cues that cells experience in their native environment. We describe here an endothelium-on-a-chip that was developed for studying endothelial barrier permeability in diabetic and diabetic kidney disease (DKD) milieu under physiologically relevant shear stress. The fluorescently labelled macromolecular tracer flux assay was applied to obtain apparent permeability (Papp) values. We demonstrated the protective effect of shear stress in our EoaC in diabetic and DKD milieu by testing endogenous diabetic and DKD factors individually (hyperglycaemia, pro inflammatory factor TNF[a], and hypertension-related hormone aldosterone) and in combination (aldosterone in hyperglycaemia, as well as a DKD mix consisting of TNF[a] and aldosterone in hyperglycaemia). To assess the applicability of our microfluidic EoaC for drug testing, we added the mineralocorticoid receptor antagonist, finerenone, and observed a statistically significant protective effect of this pharmaceutical on endothelial barrier integrity in DKD milieu in our model system. We conclude that this EoaC can be applied for endothelial barrier permeability evaluation not only in diabetic and DKD milieu, but in various pathophysiological situations. Moreover, it has shown a potential to be used in drug testing targeted to improve endothelial barrier resilience.