Development of High Throughput Applications for Renal Organoids.
Renal organoids are patient derived three-dimensional multicellular renal epithelial structures that mimic tissue function ex vivo and can be expanded almost unlimitedly. Renal organoid cultures can be derived from renal biopsy tissue and also non-invasively from patient urine. Preliminary experiments have shown that epithelial morphology and function of renal organoid tissue can be evaluated in a standardized fashion using Organoplates©. The characteristics of the renal organoids combined with a standardized evaluation assay holds promise for not only high throughput screening of drugs for function and toxicity, but also for personalized medicine. In collaboration with the HUB and Mimetas we aim to build a biobank for renal organoids, both from patients with genetic diseases as well as healthy controls. Using this biobank we aim to set up standardized assays for epithelial function and viability to test the effect of pharmaceutical compounds (e.g. diuretics) on specific renal epithelial function (e.g. sodium transport) and renal toxicity respectively. Another application for these organoids are the development of implantable cellularized devices, which could act as bioartificial kidneys and actively transport uremic toxins from the bloodstream to the urine. To do so, these cells will be tested in co-culture with endothelial cells in 3D-printed scaffold for their proliferation and functionality initially in vitro and afterwards in vivo using the Chorioallantoic Membrane Assay (CAM) as an model for vasculature ingrowth and angiogenesis.
Techniques: Organoid culture, 3D-printing, Transport assays, Imaging techniques