Kidney on a Chip Development and Drug Efficacy Testing for Renal Hypoxic Reperfusion Injury

Abstract

The microphysiological system (MPS), dynamic complex cell culture technology has the ability to mimic the human pathophysiological system. The main goal of MPS is to recreate physiologically relevant human diseases to improve drug efficacy and unknown mechanism of disease conditions. The significance of MPS is to mimic the human pathophysiological system to replace animals, patient-relevant data, high precision-low toxicity, and save money and time. Moreover, animal models have limitations to mimic human physiology and human disease conditions. The MPS has the capacity to perform conventional bioassays including western blot, ELISA, qRT-PCR, flow cytometry, biochemical assays and embedded sensors assays. Human kidneys are responsible for filtration, filtering blood and removing waste materials, the kidney is the vital organ for drug screening, efficacy, and toxicity studies. The hypoxic condition can affect renal function, predominantly homeostasis, blood pressure, the balance of electrolytes, body fluids and pH. Finally, the hypoxic condition leads to chronic kidney disease (CKD) and other organ diseases as well. The renal hypoxic condition is challenging to perform in an animal model due to the lack of a human pathophysiological system, ethical concerns, intraspecies genetic variations, lack of robustness, and time and money. This thesis work encloses the advancement of the microphysiological system for renal hypoxic reperfusion injury model and drug efficacy test to overcome the current limitations of an animal model. Renal MPS was incorporated with impedance-based transepithelial-endothelial electrochemical resistance (TEER) for real-time monitoring of renal normoxic conditions, hypoxic conditions, and drug efficacy. Furthermore, TEER data was incorporated with conventional assays for further validation. This thesis can serve as a replacement for animals to improve drug discovery and disease models.