Renal Hypoxic Reperfusion Injury-on-Chip Model for Studying Combinational Vitamin Therapy

Abstract

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.

Revolutionizing drug development: harnessing the potential of organ-on-chip technology for disease modeling and drug discovery

“…They also examined the secretion of several biomarkers, including KIM-1, HSP70, IL-6, and ET-. This study provides insights into developing a treatment for RHR injury (Chethikkattuveli Salih et al, 2022). Naik and colleagues developed a renal proximal tubule-on-a-chip platform model to investigate Lowe syndrome/Dent II disease.…”

Application of microfluidic chips in the simulation of the urinary system microenvironment

“…Chethikkattuveli et al. [ 109 ] established a microfluidic renal hypoxia-reperfusion (RHR) model using hypoxia and oxygenated cell culture medium, in which primary HPTECs and human endothelial cells were cultured on the top and basal side of the porous membrane. The disease model was validated by detecting its specific hypoxia biomarkers.…”

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