A5077377559- Renal and related cancers
- Extracellular vesicles in disease
- Biomedical Research and Pathophysiology
- Genetic and Kidney Cyst Diseases
- Neonatal Health and Biochemistry
- Pluripotent Stem Cells Research
- Ion Transport and Channel Regulation
- Renal cell carcinoma treatment
- Amino Acid Enzymes and Metabolism
- Electrolyte and hormonal disorders
- Cancer Genomics and Diagnostics
- Renal Diseases and Glomerulopathies
- Organ Donation and Transplantation
- 3D Printing in Biomedical Research
- Methemoglobinemia and Tumor Lysis Syndrome
- Cancer Cells and Metastasis
- AI in cancer detection
- Pancreatic and Hepatic Oncology Research
- Wnt/β-catenin signaling in development and cancer
- Tissue Engineering and Regenerative Medicine
- Polyomavirus and related diseases
- Hedgehog Signaling Pathway Studies
Royal Netherlands Academy of Arts and Sciences
2020-2024
University Medical Center Utrecht
2019-2024
Hubrecht Institute for Developmental Biology and Stem Cell Research
2022-2024
Roche (Switzerland)
2023
Oncode Institute
2020-2022
The Netherlands Cancer Institute
2022
Abstract Kidney tumours are among the most common solid in children, comprising distinct subtypes differing many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing disease heterogeneity currently lacking. Here, we describe first paediatric cancer organoid biobank. It contains tumour matching normal kidney organoids from over 50 children with different of cancer, Wilms tumours, malignant rhabdoid renal carcinomas, congenital mesoblastic nephromas....
Kidney organoids generated from induced pluripotent stem cells (iPSC) have proven valuable for studies of kidney development, disease, and therapeutic screening. However, specific applications been hampered by limited expansion capacity, immaturity, off-target cells, inability to access the apical side. Here, we apply recently developed tubuloid protocols purify propagate epithelium d7+18 (post nephrogenesis) iPSC-derived organoids. The resulting ‘iPSC organoid-derived (iPSCod)’ tubuloids...
Nephropathic cystinosis is a severe monogenic kidney disorder caused by mutations in CTNS, encoding the lysosomal transporter cystinosin, resulting cystine accumulation. The sole treatment, cysteamine, slows down disease progression, but does not correct established renal proximal tubulopathy. Here, we developed new therapeutic strategy applying omics to expand our knowledge on complexity of and prioritize drug targets cystinosis. We identified alpha-ketoglutarate as potential metabolite...
Abstract The prevalence of end-stage kidney disease (ESKD) is rapidly increasing with the need for regenerative therapies. Adult stem cell derived tubuloids have potential to functionally mimic adult tubule, but still lack expression important transport proteins needed waste removal. Here, we investigated extracellular vesicles (EVs) obtained from matured tubular epithelial cells modulate in vitro functional maturation. We focused on organic anion transporter 1 (OAT1), one most involved...
Abstract R‐spondins (RSPOs) are influential signaling molecules that promote the Wnt/β‐catenin pathway and self‐renewal of stem cells. Currently, RSPOs emerging as clinically relevant oncogenes, being linked to cancer development in multiple organs. Although this has instigated rapid testing therapeutic antibodies targeting RSPOs, functional evidence RSPO causally drives focused primarily on intestinal tract. Here, we assess oncogenic capacity breast a direct fashion by generating...
Organoid technology is rapidly gaining ground for studies on organ (patho)physiology. Tubuloids are long-term expanding organoids grown from adult kidney tissue or urine. The progenitor state of tubuloids comes at the expense differentiation. Here, we differentiate to model distal nephron and collecting ducts, essential functional parts kidney. Differentiation suppresses traits upregulates genes required function. A single-cell atlas reveals that differentiation predominantly generates thick...
Abstract Nephropathic cystinosis is a severe monogenetic kidney disorder caused by mutations in CTNS , encoding the lysosomal transporter cystinosin, resulting cystine accumulation. The sole treatment, cysteamine, slows down disease progression, but does not correct established proximal tubulopathy. Here, we developed new therapeutic strategy applying an omics-based to expand our knowledge on complexity of and prioritize drug targets cystinosis. We identified alpha-ketoglutarate as key...
Clinical research on monogenic kidney disease (MKD) is thriving and the need for large cohorts, prospective data collection biobanking increasing. We aim to create a sustainable MKD biobank with vast amount of uniformly collected high-quality that readily available future research, an infrastructure allows recontacting participants. The GeNepher data- ongoing sample includes patients family members known and/or suspected MKD. With tiered approach participants can give broad consent including...
Kidney tubuloids are cell models that derived from human or mouse renal epithelial cells and show high similarities with their in vivo counterparts. Tubuloids grow polarized 3D, allow for long-term expansion, represent multiple segments of the nephron, as shown by gene expression pattern. In addition, form tight, functional barriers have been succesfully used drug testing. Our knowledge tubuloids, on other hand, is only minimal. this study, we further characterized differentiated them...
Abstract Recent advances in vitro culture technologies, such as adult stem cell-derived organoids, have opened up new avenues for the development of novel, more physiologic human cancer models. Such preclinical models are essential efficient translation basic research into novel treatment regimens. We succeeded growing organoids from a range pediatric solid tumors, including Wilms’ renal cell carcinomas, and different types rhabdoid tumors (i.e., AT/RT, MRT). Tumor retain many...
ABSTRACT Advanced kidney in vitro models such as organoids or tubuloids still lack the intrinsic expression of various transport proteins needed for active secretory function. Extracellular vesicles (EVs), cell-derived structures that constitute organ’s microenvironment, are known to regulate cellular processes, including development and regeneration across nephron. In this study, we propose a new application renal tubular epithelial cell EVs modulators tubuloid functional maturation by...