Renal ischemic-reperfusion injury decreases the chances
of long-term
kidney graft survival and may lead to the loss of a transplanted kidney.
During organ excision, the cycle of warm ischemia from the donor and
cold ischemia is due to storage in a cold medium after revascularization
following organ transplantation. The reperfusion of the kidney graft
activates several pathways that generate reactive oxygen species,
forming a hypoxic-reperfusion injury. Animal models are generally
used to model and investigate renal hypoxic-reperfusion injury. However,
these models face ethical concerns and present a lack of robustness
and intraspecies genetic variations, among other limitations. We introduce
a microfluidics-based renal hypoxic-reperfusion (RHR) injury-on-chip
model to overcome current limitations. Primary human renal proximal
tubular epithelial cells and primary human endothelial cells were
cultured on the apical and basal sides of a porous membrane. Hypoxic
and normoxic cell culture media were used to create the RHR injury-on-chip
model. The disease model was validated by estimating various specific
hypoxic biomarkers of RHR. Furthermore, retinol, ascorbic acid, and
combinational doses were tested to devise a therapeutic solution for
RHR. We found that combinational vitamin therapy can decrease the
chances of RHR injury. The proposed RHR injury-on-chip model can serve
as an alternative to animal testing for injury investigation and the
identification of new therapies.