- 3D Printing in Biomedical Research
- Angiogenesis and VEGF in Cancer
- Liver physiology and pathology
- Pluripotent Stem Cells Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Radiomics and Machine Learning in Medical Imaging
- Tissue Engineering and Regenerative Medicine
- Liver Disease Diagnosis and Treatment
- Mathematical Biology Tumor Growth
- COVID-19 Clinical Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Axon Guidance and Neuronal Signaling
- Respiratory viral infections research
- Drug Transport and Resistance Mechanisms
- Liver Disease and Transplantation
- Platelet Disorders and Treatments
- Congenital heart defects research
- Barrier Structure and Function Studies
- Microfluidic and Capillary Electrophoresis Applications
- T-cell and B-cell Immunology
- Receptor Mechanisms and Signaling
- Proteoglycans and glycosaminoglycans research
- Petri Nets in System Modeling
- Pharmacological Effects and Toxicity Studies
- Viral Infections and Outbreaks Research
Mimetas (Netherlands)
2023-2024
Leiden University Medical Center
2019-2024
Leiden University
2014-2020
Netherlands Metabolomics Centre
2014-2020
Centre for Human Drug Research
2015-2019
Analytical Biosciences (China)
2019
Angiogenic sprouting, the growth of new blood vessels from pre-existing vessels, is orchestrated by cues within cellular microenvironment, such as biochemical gradients and perfusion. However, many these are missing in current vitro models angiogenic sprouting. We here describe an platform that integrates both perfusion generation stable biomolecular demonstrate its potential to study more physiologically relevant sprouting microvascular stabilization. The consists array 40 individually...
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...
Current in vitro models to test the barrier function of vasculature are based on flat, two-dimensional monolayers. These monolayers do not have tubular morphology found vivo and lack important environmental cues from cellular microenvironment, such as interaction with an extracellular matrix (ECM) exposure flow. To increase physiological relevance vasculature, it is crucial implement these better mimic native three-dimensional vascular architecture. We established a robust, high-throughput...
Abstract Formation of new blood vessels by differentiated endothelial tip cells, stalk and phalanx cells during angiogenesis is an energy-demanding process. How these specialized cell phenotypes generate their energy, whether there are differences between phenotypes, unknown. This may be key to understand functions, as (1) metabolic pathways essentially involved in the regulation angiogenesis, (2) a switch has been associated with angiogenic differentiation. With use Seahorse flux analyses,...
Ebola virus, for which we lack effective countermeasures, causes hemorrhagic fever in humans, with significant case fatality rates. Lack of experimental human models is a major obstacle that hinders the development treatment strategies. Here, model syndrome microvessel-on-a-chip system and demonstrate its applicability to drug studies. Luminal infusion virus-like particles leads albumin leakage from engineered vessels. The process mediated by Rho/ROCK pathway associated cytoskeleton...
To advance pre-clinical vascular drug research, in vitro assays are needed that closely mimic the process of angiogenesis vivo. Such should combine physiological relevant culture conditions with robustness and scalability to enable screening. We developed a perfused 3D assay includes endothelial cells (ECs) from induced pluripotent stem (iPSC) assessed its performance suitability for anti-angiogenic Angiogenic sprouting was compared primary ECs showed microvessels iPSC-EC exhibit similar...
We present a continuous-flow microelectroextraction flow cell that allows for electric field enhanced extraction of analytes from large volume (1 mL) continuously flowing donor phase into micro stagnant acceptor (13.4 μL). demonstrate the first time interface between and fast-flowing can be stabilized by phaseguide. Chip performance was assessed visual experiments using crystal violet. Then, mixture acylcarnitines off-line coupling to reversed liquid chromatography coupled time-of-flight...
Pre-clinical drug research of vascular diseases requires in vitro models vasculature that are amendable to high-throughput screening. However, current screening have sufficient throughput only limited physiological relevance, which hinders the translation findings from vivo. On other hand, microfluidic cell culture platforms shown unparalleled relevancy vitro, but often lack required throughput, scalability and standardization. We demonstrate a robust platform study angiogenesis endothelial...
Abstract This study provides a method to assess the impact of circulating plasma factors on microvascular integrity by using recently developed microvessel‐on‐a‐chip platform featuring human endothelium that is partly surrounded extracellular matrix. The system high‐throughput, which allows parallel analysis organ‐level microvessel pathophysiology, including vascular leakage. Ethylenediaminetetraacetic acid samples are mixed with inhibitors for recalcification avoid activation coagulation‐...
Endothelial cell (EC) dysfunction in response to circulating plasma factors is a known causal factor many systemic diseases. However, no appropriate assay available investigate this causality
Tumor angiogenesis concerns the development of new blood vessels supplying necessary nutrients for further existing tumor cells.The entire process is complex, involving production and consumption chemicals, endothelial cell transitions as well interactions, divisions, migrations.Microfluidic culture platform has been used to study cells derived from human induced pluripotent stem (iPSC-ECs) a physiological relevant micro-environment.In this paper, we elaborate on how define pipeline...
Abstract Liver cancer, or hepatocellular carcinoma (HCC), is a formidable malignancy characterized by the uncontrolled growth of cells within liver tissue. It represents global health concern, with risk factors including chronic viral infections (such as hepatitis B and C), excessive alcohol consumption, fatty disease, certain genetic conditions. The silent progression HCC complicates early detection, emphasizing need for deeper understanding tumor microenvironment, which plays crucial role...
Abstract Drug discovery for complex liver diseases faces alarming attrition rates. The lack of non-clinical models that recapitulate key aspects (patho)-physiology is likely contributing to the inefficiency developing effective treatments. Of particular notice common omission an organized microvascular component despite its importance in maintaining function and involvement development several pathologies. Increasing complexity vitro usually associated with a scalability robustness which...
We studied PUUV infection in high-throughput 3D endothelial vessels-on-chip, that more closely resemble the vivo situation than static 2D cultures. In these vessels, increased monocyte adhesion, but not vascular permeability.
Abstract Drug discovery for complex liver diseases faces alarming attrition rates. The lack of non-clinical models that recapitulate key aspects (patho)-physiology is likely contributing to the inefficiency developing effective treatments. Of particular notice common omission an organized microvascular component despite its importance in maintaining function and involvement development several pathologies. Increasing complexity vitro usually associated with a scalability robustness which...
Abstract The transition from 2D to 3D cell culture is a first step towards more physiologically relevant in vitro cancer models. To adequately capture the complex tissue architectures observed vivo, microfluidic techniques incorporate and achieve long-term gradient stability, continuous perfusion patterning of layers as stratified co-cultures. We used standardized high-throughput (n=40) platform called OrganoPlate® generate precisely controlled gradients, without pumps, ideal for growing...
Pre-clinical drug research of vascular diseases requires in vitro models vasculature that are amendable to high-throughput screening. However, current screening have sufficient throughput only limited physiological relevance, which hinders the translation findings from vivo. On other hand, microfluidic cell culture platforms shown unparalleled relevancy vitro, but often lack required throughput, scalability and standardization. We demonstrate a robust platform study angiogenesis endothelial...