Leiden, Decmber 30, 2024 — Researchers from MIMETAS and Sanofi have published a study on an immunocompetent human kidney-on-a-chip model.
Kidney damage and dysfunction are significant health issues worldwide, contributing to high morbidity and mortality. Chronic kidney disease (CKD) affects 10-15% of the population in Western countries and often progresses to end-stage renal disease (ESRD), requiring dialysis or transplantation. Current treatments primarily address symptoms rather than causes, highlighting the need for efficient preclinical research tools to improve understanding and support drug development.
The study introduces a sophisticated human immunocompetent 3D in vitro co-culture model of the proximal tubule using MIMETAS' OrganoPlate® platform. This high-throughput microfluidic platform co-cultures renal proximal tubule epithelial cells (RPTECs) and human umbilical vein endothelial cells (HUVECs) under flow conditions, closely mimicking the human kidney environment. Including human primary monocytes from different donors creates an immunocompetent setting, enabling the study of interactions between renal and immune cells, crucial for understanding renal inflammation and diseases.
Renal inflammation was successfully induced using complement activated serum (CAS), shown through epithelial morphological changes, increased expression of adhesion molecules, release of pro-inflammatory cytokines, and reduced epithelial viability. The real-time observation of monocyte migratory behavior revealed increased extravasation and migration towards the renal compartment upon CAS exposure, with donor variations. This model also proved effective for testing immune modulatory compounds, demonstrating inhibition of monocyte migration under inflammatory conditions.
The OrganoPlate® platform's compatibility with automation and high throughput makes it ideal for drug development. Its versatility allows modulation of environmental factors and incorporation of various cell types, providing significant advantages over traditional animal models. This capacity for precise control of experimental conditions highlights the platform's potential to revolutionize preclinical research.
The kidney-on-a-chip model developed by MIMETAS and Sanofi bridges a critical gap in renal disease research, offering a robust platform for studying immune-mediated kidney injuries and testing therapeutic interventions at scale. This advancement paves the way for more effective and tailored treatments for patients with chronic kidney diseases.
