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

Abdul Rahim Chethikkattuveli Salih, Arun Asif, Anupama Samantasinghar, Hafiz Muhammad Umer Farooqi, Sejoong Kim, Kyung Hyun Choi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Pages (from-to)3733-3740
Number of pages8
JournalACS Biomaterials Science and Engineering
Volume8
Issue number9
DOIs
StatePublished - 12 Sep 2022

Keywords

  • ascorbic acid
  • reactive oxygen species
  • renal hypoxic-reperfusion injury
  • renal proximal tubular epithelial cell
  • retinol

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