A5036441925- Biomedical Research and Pathophysiology
- Neonatal Health and Biochemistry
- Amino Acid Enzymes and Metabolism
- Drug Transport and Resistance Mechanisms
- Renal and related cancers
- 3D Printing in Biomedical Research
- Dialysis and Renal Disease Management
- Pharmacological Effects and Toxicity Studies
- Tissue Engineering and Regenerative Medicine
- Ion Transport and Channel Regulation
- Erythrocyte Function and Pathophysiology
- Chemotherapy-induced organ toxicity mitigation
- Metabolism and Genetic Disorders
- Innovative Microfluidic and Catalytic Techniques Innovation
- Organ Donation and Transplantation
- Acute Lymphoblastic Leukemia research
- Genetic and Kidney Cyst Diseases
- Pharmacogenetics and Drug Metabolism
- Renal Diseases and Glomerulopathies
- Chronic Kidney Disease and Diabetes
- Acute Kidney Injury Research
- Polyamine Metabolism and Applications
- Muscle and Compartmental Disorders
- Pluripotent Stem Cells Research
- Magnesium in Health and Disease
Radboud University Nijmegen
2011-2021
Radboud University Medical Center
2010-2021
Radboud Institute for Molecular Life Sciences
2014-2021
Pharmo Institute
2018
Centre for Biomedical Network Research on Rare Diseases
2018
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2018
Instituto de Investigación Sanitaria Aragón
2018
Universidad Carlos III de Madrid
2018
Hospital Universitario Fundación Jiménez Díaz
2018
Technische Universität Berlin
2018
Reabsorption of filtered solutes from the glomerular filtrate and excretion waste products xenobiotics are main functions renal proximal tubular (PT) epithelium. A human PT cell line expressing a range functional transporters would help to augment current knowledge in physiology pharmacology. We have established characterized conditionally immortalized epithelial (ciPTEC) obtained by transfecting subcloning cells exfoliated urine healthy volunteer. The origin this has been confirmed...
Abstract The development of a biotechnological platform for the removal waste products (e.g. uremic toxins), often bound to proteins in plasma, is prerequisite improve current treatment modalities patients suffering from end stage renal disease (ESRD). Here, we present newly designed bioengineered tubule capable active toxin secretion through concerted action essential transporters, viz. organic anion transporter-1 (OAT1), breast cancer resistance protein (BCRP) and multidrug protein-4...
Proximal tubules in the kidney play a crucial role reabsorbing and eliminating substrates from body into urine, leading to high local concentrations of xenobiotics. This makes proximal tubule major target for drug toxicity that needs be evaluated during development process. Here, we describe an advanced vitro model consisting fully polarized renal tubular epithelial cells cultured microfluidic system. Up 40 leak-tight were on this platform provides access basolateral as well apical side...
Drug-induced nephrotoxicity still hampers drug development, because current translation from in vitro or animal studies to human lacks high predictivity. Often, renal adverse effects are recognized only during clinical stages of development. The study aimed establish a robust and more complete cell model suitable for screening drug-related interactions nephrotoxicity. In addition endogenously expressed organic cation transporters efflux transporters, conditionally immortalized proximal...
Abstract The bioartificial kidney (BAK) aims at improving dialysis by developing ‘living membranes’ for cells-aided removal of uremic metabolites. Here, unique human conditionally immortalized proximal tubule epithelial cell (ciPTEC) monolayers were cultured on biofunctionalized MicroPES (polyethersulfone) hollow fiber membranes (HFM) and functionally tested using microfluidics. Tight monolayer formation was demonstrated abundant zonula occludens-1 (ZO-1) protein expression along the tight...
Proximal tubule epithelial cells (PTEC) are susceptible to drug-induced kidney injury (DIKI). Cell-based, two-dimensional (2D) in vitro PTEC models often poor predictors of DIKI, probably due the lack physiological architecture and flow. Here, we assessed a high throughput, 3D microfluidic platform (Nephroscreen) for detection DIKI pharmaceutical development. This system was established with four model nephrotoxic drugs (cisplatin, tenofovir, tobramycin cyclosporin A) tested eight compounds....
Drug-transporter interactions could impact renal drug clearance and should ideally be detected in early stages of development to avoid toxicity-related withdrawals later stages. This requires reliable robust assays for which current high-throughput screenings have, however, poor predictability. Kidney-on-a-chip platforms have the potential improve predictability, but often lack compatibility with high-content detection platforms. Here, we combined conditionally immortalized proximal tubule...
Receptor-mediated endocytosis, involving megalin and cubilin, mediates renal proximal-tubular reabsorption is decreased in Dent disease because of mutations the chloride/proton antiporter, chloride channel-5 (CLC-5), resulting low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, failure. To facilitate studies receptor-mediated endocytosis role CLC-5, we established conditionally immortalized epithelial cell lines (ciPTECs) from three patients with CLC-5 (30:insH, R637X,...
Background and Purpose Recently, two phase‐II trials demonstrated improved renal function in critically ill patients with sepsis‐associated acute kidney injury treated the enzyme alkaline phosphatase. Here, we elucidated dual active effect on protection of Experimental Approach The human recombinant phosphatase (recAP) LPS‐induced was studied Sprague–Dawley rats. Renal assessed by transcutaneous measurement FITC‐sinistrin elimination freely moving, awake mechanism action recAP further...
Kidney disease modeling and assessment of drug-induced kidney injury can be advanced using three-dimensional (3D) microfluidic models that recapitulate in vivo characteristics. Fluid shear stress (FSS) has been depicted as main modulator improving vitro physiology proximal tubule epithelial cells (PTECs). We aimed to elucidate the role FSS primary cilia on transport activity morphology PTECs.Human conditionally immortalized PTEC (ciPTEC-parent) was cultured a 3D device, OrganoPlate, under...
Background Chronic kidney disease (CKD) is characterized by the progressive accumulation of various potential toxic solutes. Furthermore, uremic plasma a complex mixture hampering accurate determination toxin levels and identification novel Methods In this study, we applied 1H-nuclear magnetic resonance (NMR) spectroscopy, following three distinct deproteinization strategies, to determine differences in metabolic status stage 3–4 CKD patients healthy controls. Moreover, human renal proximal...