KNOVV · Kidney Nephron Orientation in Vivo-like in Vitro

KNOVV aims at directing nephron spatial orientation within renal organoids to mimic in vivo kidney development.Chronic kidney disease (CKD) is an increasing socio-economic burden, with 100 million people affected in Europe; available treatments are limited to dialysis and transplants. Tissue engineering and regenerative medicine (TERM) aims at developing in vivo–like organs, using in vitro three-dimensional (3D) systems as new therapies. Promising TERM therapies involving self-organized renal organoids from human induced pluripotent stem cells (hiPSC) are being investigated. These kidney organoids contain the appropriate cells although heterogeneity, immature stage and lack of the spatially specific nephron orientation are still major bottlenecks. These limitations impair microphysiological form and function, which limits their research utility and clinical applications. I hypothesize that inducing spatial nephron orientation in kidney organoids will result in improved maturation and function closely mimicking the in vivo organ. To achieve this, I will optimize protocols to generate renal organoids from hiPSC. I will identify molecules to inhibit or induce glomerulogenesis (glomeruli formation), and develop glomerulogenesis-inducing and -inhibiting hydrogels for bioprinting renal organoids. Immunostaining, qPCR, and functional assays will be used to evaluate the morphology and function of the 3D bioprinted renal organoid construct. KNOVV will strengthen my research and academic profiles, broaden my knowledge and experience by combining developmental biology, TERM and biofabrication to improve renal organoids. My ambition is that the bioprinted renal organoid constructs with spatially directed nephrons will enable unprecedented microphysiological maturation and function. This will allow a leap beyond the current organoids state of art and ultimately lead us closer to clinical translation, offering an alternative for the growing CKD population.