ABS 108: Multi Kidney Disease Modelling using hiPSC-Derived Biomimetic Glomerulus-on-a-Chips

Anavi Kaul ¹ , Yize Zhang ¹ , Amanda Barreto ¹ , Bowen Jiang ¹ , Samira Musah ¹ ² ³ ⁴ ⁵ ⁶

¹ Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA
² Department of Medicine, Division of Nephrology, Duke University School of Medicine, Durham, NC, USA
³ Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA
⁴ Center for Biomolecular and Tissue Engineering, Duke University, Durham, NC, USA
⁵ Affiliate Faculty of the Developmental and Stem Cell Biology Program, Duke University School of Medicine, Durham, NC, USA
⁶ MEDx Investigator, Duke University, Durham, NC, USA

Van Wickle (2025) Volume 1, ABS 108

Abstract: More than 1 in 7 adults in the US have Chronic Kidney Disease (CKD), a condition marked by progressive kidney function loss. An organ-on-a-chip is a microfluidic device that mimics the structure and function of human organs - our lab's glomerulus-on-a-chip allows us to study CKD and related injuries in a controlled, physiologically relevant environment. We are investigating four injury models—adriamycin (ADR), liposaccharide (LPS), diabetic nephropathy, and pamidronate (PAM)—to identify common molecular mechanisms and early podocyte injury biomarkers using a multiomics approach. The ultimate goal is to design gene circuits that respond to key biomarkers and protect podocytes under injury conditions. The chip is developed through a multi-week process, involving PDMS casting, electrospinning silk fibroin membranes, and seeding with endothelial and intermediate mesoderm cells, which differentiate into podocytes. Functional assays track plasma protein filtration (albumin and inulin)—from the bottom to top channel of our chip to represent the transition from blood to urine—using fluorescent spectrometry at key time points to monitor injury progression. Key findings show significant podocyte injury occurs only when inflammation is present alongside high glucose, emphasizing the role of cytokines like TNF-α. PAM and ADR both increase filtration, with PAM acting within 2 days and ADR after 5 days, while LPS has minimal impact. HG alone does not significantly alter filtration, suggesting inflammation is necessary for damage. Next steps include refining filtration timepoints (HGIT at 12h–72h, PAM at 12h–120h, ADR at 48h–120h) and performing molecular assays targeting inflammatory (NF-κB) and structural (Rho/Rac/CDC41) pathways to clarify podocyte injury mechanisms.