Abstract: SA-PO0270
Novel Three-Dimensional (3D) Human Kidney Proximal Tubular Epithelial Tissue Model for In Vitro Drug Screening
Session Information
- AKI: Mechanisms - Cell Signaling
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Ayehunie, Seyoum, MatTek Corp, Ashland, Massachusetts, United States
- Mayo, Martha R., MatTek Corp, Ashland, Massachusetts, United States
- Neale, Dylan B., Sartorius AG, New York, New York, Germany
- Klausner, Mitchell, MatTek Corp, Ashland, Massachusetts, United States
Background
The renal proximal tubular (PT) region is the most common site of compound-specific kidney injury. This region performs essential renal functions, including the reabsorption of low-molecular-weight proteins, solutes, and glucose; secretion of acids; and clearance of administered medications. The goal of this study is to evaluate a human 3D organotypic kidney tissue model for predicting drug-induced nephrotoxicity.
Methods
Cells were isolated from human kidney explant. 3D kidney tissue models were characterized by histology, barrier integrity (transepithelial electrical resistance, TEER), immunohistochemistry, and qPCR. The HPTEC organotypic tissues showed characteristic tubular structures, developed functional barrier properties with TEER values reaching 90 Ohmxcm2 by day 12, staining was used to identify ZO-1, claudin-1, and occludin.
Results
The differentiated tissue model expressed brush border proteins megalin, villin, and GGT1, along with the water channel AQP1 on the apical surface and the sodium-potassium ATPase pump on the basolateral side. qPCR analysis confirmed the expression of a comprehensive panel of HPTEC-specific markers, influx and efflux transporters, and drug-metabolizing enzymes necessary for renal drug clearance, secretion, and reabsorption. After confirming organ-like functionality, acute toxicity studies were performed using seven model drugs at 8 concentrations each. Acute exposure to clinically relevant BMS-986094 (INX-0891), anti-hepatitis C drug that was discontinued during clinical trials due to severe kidney and heart toxicity, resulted in reduced TEER and MTT, in a concentration-dependent manner. A positive control compound Cisplatin and the antifungal medication amphotericin B also decreased TEER and tissue viability while increasing LDH release. In contrast, no adverse effects were noted with the negative control acarbose. EC50 values were calculated in real time using Incucyte image analyzer.
Conclusion
In summary, the in vitro 3D kidney tissue closely resembles the in vivo human PT region in morphology, barrier function, gene expression, and overall tissue performance. Such a model aligns well with FDA Modernization Act 3.0 guidelines and represents an important advancement in new approach methodologies (NAMs) aimed at identifying adverse renal effects of therapeutic candidates while reducing animal experimentation.
Acknowledgment
None