Using Organ-on-a-Chip Co-Culture Technology to Explore the Pathophysiology of Tubulopathies: A Paradigm Shift in Kidney Disease Research
- Bioengineering: Modeling, Diagnosis, Therapy
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
- 400 Bioengineering
- Zhong, Chutong, University College London, London, United Kingdom
- Grillo, Alessandra, University College London, London, United Kingdom
- Siew, Keith, University College London, London, United Kingdom
- Walsh, Stephen B., University College London, London, United Kingdom
Group or Team Name
- London Tubular Centre.
Tubulopathies are a group of renal disorders that significantly impact patient morbidity and mortality, with limited current treatment options. The complex pathophysiology of these diseases hampers our understanding, resulting in a pressing need for advanced, physiologically relevant models. This research harnesses Organ-On-a-Chip (OOaC) technology to simulate human tubular physiology, thus elucidating the pathogenesis of tubulopathies and potentially facilitating development of novel therapeutic strategies.
Urine-derived renal tubular epithelial cells (uRTEC) and blood outgrowth endothelial cells (BOEC) were isolated from urine and blood samples collected from healthy volunteers and patients from tubular clinic by methods previously described (Ormiston et al., 2015; Ikeda et al., 2020). uRTEC and BOEC cells were applied adjacently in a three-lane microfluidic chip platform OrganoPlate following manufacture’s protocol with modifications on the constitution of the extracellular matrix gel.
Patient-derived renal tubules and blood vessel endothelium formed in the OrganoPlate channel on an average of 7-10 days of culture. Barrier integrity assay in the OrganoPlate using fluorescent probes confirmed tight junctions between cells. qPCR of the cell lysate showed these tubules expressed the distal convoluted tubule specific marker NCC (SLC12A3).
These preliminary data demonstrate that patient-derived uRTEC and BOEC were able to form tubule/blood vessel-like structures in the OrganoPlate. Given these samples are primary cells from patients, we propose this OOaC model will dynamically reflect in vivo human renal physiology with tubule-capillary interaction. We highlight the potential of OOaC culture systems combined with patient-derived cells to uncover tubulopathy. Furthermore, this innovative methodology can be employed to screen a panel of drugs, revealing varying drug efficacies and toxicity profiles individually with continuous monitoring of disease progression, ultimately bringing personalised medicine to tubular diseases.
The 3D confocal imaging of the immortalised uRTEC cells in the OOaC on Day 3 and Day 7, showing a gradual completion of the tubule in the plate.