The aim of the project “Unified organoid system for modeling kidney and heart interaction in chronic disease and its treatment” is the establishment of a novel micro-physiological system for the in vitro study of the cardiorenal axis and organ crosstalk. hiPSC-derived organoids for the heart and kidney counterpart are being generated and coupled in a microfluidic “cardiorenal unit” with the intention to identify, characterize and counteract the mediators of cellular damage leading to disease.
Gold standard protocols for the generation of the two organoids allowed to achieve and co-culture functional tissue with a big discrepancy in size. Kidney organoids are one hundred times bigger than cardiac microtissues, hence limiting the rendering of a physiologically relevant model and the execution of higher throughput experiments through miniaturization.
Advanced biofabrication techniques like 3D bioprinting have already shown to be effective in the generation of micro-kidney organoids, making them comparable in size with cardiac microtissues.
Impact
For the first time reported, heart and kidney organoids were successfully co-cultured in dynamic culture conditions while retaining their morphology and organ-specific function. The establishment of this advanced in vitro micro-physiological system represents a step forward towards the integration of biology and engineering, which is essential to achieve a higher level of complexity and more physiologically relevant disease modeling.
reNEW research
Third year PhD student now focusing on the identification and measure of crosstalk between hiPSC-derived heart and kidney organoids using the newly developed system.
Image description
Kidney organoids are obtained from undifferentiated hiPSCs and start forming nephron structures after mesodermal induction, as they are switched to an air-liquid interface culture. The immunofluorescent image represents a miniaturized, printed kidney organoid demonstrating anatomically correct interconnected segments of the nephron: glomerulus (red), proximal tubule (green) and distal tubule (cyan). Acquired with the Leica SP8 WLL1 microscope. Scale bar: 50 µm.
Credits
Beatrice Gabbin, Bellin lab, Rabelink lab, reNEW Leiden, The Netherlands.
