Abstract: TH-PO0035
Glomerulus-Tubule Integrated Kidney-on-a-Chip Platform for Preclinical Evaluation of Chemotherapy-Induced Nephrotoxicity and Therapeutic Interventions
Session Information
- Bioengineering: MPS, Flow, and Delivery
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bioengineering
- 400 Bioengineering
Authors
- You, Eun Mi, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea (the Republic of)
- Park, Seokwoo, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Korea (the Republic of)
Background
While glomerulus-on-a-chip and tubule-on-a-chip technologies mimic glomerular and tubular functions, an integrated model combining both has not been reported. Anticancer drug-induced nephrotoxicity is a common clinical issue with limited treatments. Here, we developed an integrated glomerulus-tubule kidney-on-a-chip and established nephrotoxicity models using anticancer agents. We evaluated toxicity and candidate therapeutics to demonstrate the platform’s potential for predicting and replacing clinical trials.
Methods
We evaluated the performance of the integrated chip by comparing it to a static transwell model, assessing the expression of Aquaporin 1, Na/K ATPase, OCT2, and Nephrin. Nephrotoxicity was modeled by applying chemotherapeutic agents known to preferentially affect specific nephron segments: Cisplatin and Oxaliplatin predominantly affecting the tubule, and Sunitinib primarily targeting the glomerulus, each for 48 hours. Cimetidine, a tubule-protective agent, and Sildenafil, a glomerulus-targeted therapeutic, were administered to evaluate potential protective effects. Functional integrity and injury were assessed using TEER, CCK-8, and albumin permeability.
Results
In microfluidic-chip cultures, selected proximal-tubule markers AQP1 and OCT2 and podocyte marker nephrin all showed higher expression than in respective static conditions. Cisplatin treatment led to a marked decrease in TEER and cell viability in the tubule, which were restored by Cimetidine co-treatment. Oxaliplatin similarly reduced TEER and viability, with recovery observed mainly in the tubule compartment following cimetidine co-treatment. Sunitinib caused decreased TEER, reduced viability, and increased albumin permeability. Sildenafil treatment did not yield meaningful improvement in TEER or viability, but tended to reduce albumin permeability.
Conclusion
This study developed an integrated glomerulus-tubule kidney-on-a-chip and established chemotherapy-induced nephrotoxicity models. Therapeutic effects were experimentally validated using the chip, which shows promise as a preclinical tool for toxicity and drug efficacy evaluation.