Program coordinators

Upcoming meetings

• 27 February (10-16h, Radboudumc)
• 25 September (10-16h, UMCU)

Previous meetings

• 28 September 2023 (13-16:45h, Online)
• 16 march 2023 (UU)

Challenges

To mimic the structural, cellular and functional complexity of the kidney and to address the remote connection/ interactions with other organs via metabolic regulations several issues need to be resolved:

• Maturation of kidney organoids
• Differentiation and isolation of different cell types
• Physiological consideration related to kidney function (urine formation, albumin reabsorption, glomerular filtration and tubular secretion)
• Replicating the interstitial space that supports the vasculature and the tubular system of the nephron
• Perfusable systems to assess transepithelial transport of (toxic) compounds

Collaboration partners

• National: RegMedXB, MDR, Proefdiervrij, Dutch Kidney Foundation, NBTE
• International: European Society of Artificial Organs (ESAO), European Renal Association – European Dialysis and Transplant Association (ERA-EDTA), TERMIS, International Society for Biofabrication (ISB), American Society of Nephrology (ASN), The European Organ-on-Chip Society (EUROoCS)
• Printing/ microfluidics companies: Poietis, RegenHu, Cellink/BICO, Readily3D, Aspect Biobioprinting, Mimetas, Allevi, Dolomite

Background

Chronic kidney disease (CKD) is a healthcare problem worldwide and affects about 10% of the adult population in the USA [1]. CKD often leads to low glomerular filtration rate, high urinary albumin excretion, interstitial fibrosis, anemia, hyperphosphatemia and additional complications like cardiovascular disease and hypertension [2]. The typical pathological progression of CKD is gradual, irreversible loss of nephrons, the distinct functional compartments of kidneys [3]. The process of nephrogenesis, the formation of new nephrons, ceases shortly before birth [4] Thus, the loss of nephrons can only be attenuated but not reversed, and eventually results in end-stage kidney disease (ESKD) [5].

Generally, the only therapeutic options for patients with ESRD are dialysis or kidney transplantation. Life-long dialysis reduces the quality of life and has side effects such as hypotension, high infection rate, and loss of erythropoietin and activated vitamin D. In addition, there are problems related to transplantation including donor organ shortage, transplant rejection, high cost, increased infections and potential tumor formation caused by immunosuppression [6].

The kidney is a complex organ and consists of over 20 different types of cells which are constructed into individual anatomical and functional units including the glomerulus, and proximal and distal tubules. The structural and functional unit of the kidney, the nephron, is engaged in highly specialized functions via the coordinated activity of transporters and response mechanism, making susceptible to injury (e.g. drug- induced, diabetes, etc).

The growing number of CKD/ESRD cases and the shortage of transplantable kidneys have caused increasing interest in renal regenerative treatment, renal disease models and bioartificial kidneys [7]. Drug injury assessment relies heavily on experimental animal models, and it is difficult to precisely reflect the same predictive capacity in humans. In recent years, various protocols have been developed to establish cell lines capable of reproducing important metabolic and solute transport function of the kidney [8,9] for drug screening purposes and as cell components for the bioartificial kidney [10].  Meanwhile, the differentiation of human pluripotent stem cells (hPSCs), such as human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) into different renal-like cell types and self-organizing kidney organoids has been extensively documented. At the moment, the maturation degree of the kidney organoids is primitive, thus, efforts are made to improve their commitment to functional nephrons [11, 12].