A5027838810- 3D Printing in Biomedical Research
- Pluripotent Stem Cells Research
- Cell Adhesion Molecules Research
- Tissue Engineering and Regenerative Medicine
- Angiogenesis and VEGF in Cancer
- Congenital heart defects research
- Barrier Structure and Function Studies
- Renal and related cancers
- Neuroscience and Neural Engineering
- DNA Repair Mechanisms
- Single-cell and spatial transcriptomics
- Cellular Mechanics and Interactions
- CRISPR and Genetic Engineering
- Electrospun Nanofibers in Biomedical Applications
- Cell Image Analysis Techniques
- Innovative Microfluidic and Catalytic Techniques Innovation
- Cancer Cells and Metastasis
- CAR-T cell therapy research
- Microfluidic and Capillary Electrophoresis Applications
- Mitochondrial Function and Pathology
- Zebrafish Biomedical Research Applications
- Immune cells in cancer
- Congenital Heart Disease Studies
- Cardiomyopathy and Myosin Studies
- Vascular Anomalies and Treatments
Leiden University Medical Center
2015-2025
Leiden University
2016-2024
Southern Federal University
2024
National Institutes of Health
2005-2023
National Cancer Institute
2006-2023
University of Oxford
2019
Royal Netherlands Academy of Arts and Sciences
2017
University of Glasgow
2017
Cancer Genomics Centre
2013-2014
Heidelberg University
2006-2011
Cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) are functionally immature, but this is improved by incorporation into engineered tissues or forced contraction. Here, we showed that tri-cellular combinations of hiPSC-derived CMs, cardiac fibroblasts (CFs), and endothelial also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs MTs with CFs sarcomeric structures T-tubules, enhanced contractility, mitochondrial...
Cardiomyocytes and endothelial cells in the heart are close proximity constant dialogue. Endothelium regulates size of heart, supplies oxygen to myocardium secretes factors that support cardiomyocyte function. Robust predictive cardiac disease models faithfully recapitulate native human physiology vitro would therefore ideally incorporate this cardiomyocyte-endothelium crosstalk. Here, we generated characterized microtissues integrate both cell types complex 3D structures. We established...
Human neutrophil-specific CD177 (NB1 and PRV-1) has been reported to be up-regulated in a number of inflammatory settings, including bacterial infection granulocyte-colony-stimulating factor application. Little is known about its function. By flow cytometry immunoprecipitation studies, we identified platelet endothelial cell adhesion molecule-1 (PECAM-1) as binding partner CD177. Real-time protein-protein analysis using surface plasmon resonance confirmed cation-dependent, specific...
Objective— Endothelial cells (ECs), pericytes, and vascular smooth muscle (vSMCs) are essential for development, their dysfunction causes multiple cardiovascular diseases. Primary research are, however, difficult to obtain. Human-induced pluripotent stem (hiPSCs) derived from somatic tissue a renewable source of ECs vSMCs; use as disease models has been limited by low inconsistent efficiencies differentiation the lack phenotypic bioassays. Approach Results— Here, we developed defined...
Mammalian ALDH7A1 is homologous to plant ALDH7B1, an enzyme that protects against various forms of stress, such as salinity, dehydration, and osmotic stress. It known mutations in the human <i>ALDH7A1</i> gene cause pyridoxine-dependent folic acid-responsive seizures. Herein, we show for first time hyperosmotic stress by generating osmolytes metabolizing toxic aldehydes. Human expression Chinese hamster ovary cells attenuated stress-induced apoptosis caused increased extracellular...
We recently reported that junctional adhesion molecule (JAM)-C plays a role in leukocyte transendothelial migration. Here, the of JAM-C vascular permeability was investigated vitro and vivo. As opposed to macrovascular endothelial cells constitutively expressed cell–cell contacts, quiescent microvascular cells, localized mainly intracellularly, recruited junctions upon short-term stimulation with growth factor (VEGF) or histamine. Strikingly, disruption function decreased basal prevented...
Organs-on-chips are microengineered in vitro tissue structures that can be used as platforms for physiological and pathological research. They provide tissue-like microenvironments which different cell types co-cultured a controlled manner to create synthetic organ mimics. Blood vessels an integral part of all tissues the human body. Development vascular is therefore important research topic advancing field organs-on-chips since generated will require blood or nutrient supply. Here, we have...
Significance Anthracyclines like doxorubicin are anticancer drugs, used by over 1 million cancer patients annually. However, they cause severe side effects, most notably, cardiotoxicity and therapy-related malignancies. It is unclear whether these effects directly linked to their activity. Doxorubicin exerts two activities: DNA damage chromatin damage. Here, we show that both activities conspire in the cardiotoxicity, while variants with only chromatin-damaging activity remain active drugs...
A renewable source of human monocytes and macrophages would be a valuable alternative to primary cells from peripheral blood (PB) in biomedical research. We developed an efficient protocol derive induced pluripotent stem (hiPSCs) performed functional comparison with PB-derived cells. hiPSC-derived were after cryopreservation exhibited gene expression profiles comparable monocytes. Notably, more activated greater adhesion endothelial under physiological flow. successfully polarized M1 M2...
Crosstalk between endothelial cells (ECs) and pericytes or vascular smooth muscle (VSMCs) is essential for the proper functioning of blood vessels. This balance disrupted in several diseases but there are few experimental models which recapitulate this cell dialogue humans. Here, we developed a robust multi-cell type 3D vessel-on-chip (VoC) model based entirely on human induced pluripotent stem (hiPSCs). Within fibrin hydrogel microenvironment, hiPSC-derived self-organized to form stable...
Functional vasculature is essential for delivering nutrients, oxygen, and cells to the heart removing waste products. Here, we developed an in vitro vascularized human cardiac microtissue (MT) model based on induced pluripotent stem (hiPSCs) a microfluidic organ-on-chip by coculturing hiPSC-derived, pre-vascularized, MTs with vascular within fibrin hydrogel. We showed that networks spontaneously formed around these were lumenized interconnected through anastomosis. Anastomosis was fluid flow...
Physiologically relevant human models that recapitulate the challenges of solid tumors and tumor microenvironment (TME) are highly desired in chimeric antigen receptor (CAR)-T cell field. We developed a breast cancer-on-chip model with an integrated endothelial barrier enables transmigration perfused immune cells, their infiltration into tumor, concomitant monitoring cytokine release during culture over period up to 8 days. Here, we exemplified its use for investigating CAR-T efficacy...
Lipoprotein(a) [Lp(a)], consisting of LDL and the unique constituent apolipoprotein(a) [apo(a)], which contains multiple repeats resembling plasminogen kringle 4, is considered a risk factor for development atherosclerotic disorders. However, underlying mechanisms atherogenicity Lp(a) are not completely understood. Here, we define novel function in promoting inflammatory cell recruitment that may contribute to its atherogenicity. Through apo(a) moiety specifically interacts with...
Hematogenous dissemination of melanoma is a life-threatening complication this malignant tumor. Here, we identified junctional adhesion molecule-C (JAM-C) as novel player in metastasis to the lung. JAM-C expression was human and murine cell lines, melanoma, well metastatic including lung metastasis. expressed on both B16 cells endothelial promoted transendothelial migration cells. We generated mice with inactivation JAM-C. JAM-C(-/-) endothelial-specific JAM-C-deficient displayed...
Several studies have reported endothelial cell (EC) derivation from human induced pluripotent stem cells (hiPSCs). However, few explored their functional properties in depth with respect to line-to-line and batch-to-batch variability how they relate primary ECs. We therefore carried out accurate characterization of hiPSC-derived ECs (hiPSC-ECs) multiple (non-integrating) hiPSC lines compared them various assays, which included barrier function using real-time impedance spectroscopy an...