A5064317519- Pluripotent Stem Cells Research
- Tissue Engineering and Regenerative Medicine
- Congenital heart defects research
- Cardiomyopathy and Myosin Studies
- CRISPR and Genetic Engineering
- 3D Printing in Biomedical Research
- Electrospun Nanofibers in Biomedical Applications
- Pancreatic function and diabetes
- Cardiovascular Effects of Exercise
- Mitochondrial Function and Pathology
- Neuroscience and Neural Engineering
- Single-cell and spatial transcriptomics
- Lipoproteins and Cardiovascular Health
- Mesenchymal stem cell research
- Hippo pathway signaling and YAP/TAZ
- Cardiac Fibrosis and Remodeling
- Wnt/β-catenin signaling in development and cancer
- Renal and related cancers
- Gut microbiota and health
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- Spaceflight effects on biology
- Cardiac electrophysiology and arrhythmias
- Wind Turbine Control Systems
- Cardiac Health and Mental Health
Amsterdam University Medical Centers
2022-2024
University Medical Center Utrecht
2013-2023
Vrije Universiteit Amsterdam
2023
Utrecht University
2013-2022
Heidelberg University
2013-2022
University Hospital Heidelberg
2013-2022
Cardiovascular Institute of the South
2017-2021
Stanford University
2017-2021
Leiden University Medical Center
2016
Netherlands Heart Institute
2016
Rationale: The cardiac conduction system (CCS) consists of distinct components including the sinoatrial node, atrioventricular His bundle, bundle branches, and Purkinje fibers. Despite an essential role for CCS in heart development function, has remained challenging to interrogate because inherent obstacles small cell numbers, large cell-type heterogeneity, complex anatomy, difficulty isolation. Single-cell RNA-sequencing allows genome-wide analysis gene expression at single-cell resolution....
Human-induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) have risen as a useful tool in cardiovascular research, offering wide gamut of translational and clinical applications. However, inefficiency the currently available iPSC-EC differentiation protocol underlying heterogeneity derived iPSC-ECs remain major limitations technology.Here, we performed droplet-based single-cell RNA sequencing (scRNA-seq) human iPSCs after differentiation. Droplet-based scRNA-seq enables...
In mammals, cardiac development proceeds from the formation of linear heart tube, through complex looping and septation, all while increasing in mass to provide oxygen delivery demands embryonic growth. The developing must orchestrate regional differences cardiomyocyte proliferation control morphogenesis. During ventricular wall formation, compact myocardium proliferates more vigorously than trabecular myocardium, but mechanisms controlling such among populations are not understood. Control...
Since the discovery of human induced pluripotent stem cells (hiPSCs), numerous strategies have been established to efficiently derive cardiomyocytes from hiPSCs (hiPSC-CMs). Here, we describe a cost-effective strategy for subsequent massive expansion (>250-fold) high-purity hiPSC-CMs relying on two aspects: removal cell-cell contacts and small-molecule inhibition with CHIR99021. The protocol maintains CM functionality, allows cryopreservation, can be used in downstream assays such as disease...
Accidental injury to the cardiac conduction system (CCS), a network of specialized cells embedded within heart and indistinguishable from surrounding muscle tissue, is major complication in surgeries. Here, we addressed this unmet need by engineering targeted antibody-dye conjugates directed against CCS, allowing for visualization CCS vivo following single intravenous injection mice. These optical imaging tools showed high sensitivity, specificity, resolution, with no adverse effects on...
Adverse remodeling after myocardial infarction (MI) is strongly influenced by T cells. Stem cell therapy MI, using mesenchymal stem cells (MSC) or cardiomyocyte progenitor (CMPC), improved cardiac function, despite low retention and limited differentiation. As MSC secrete many factors affecting proliferation we hypothesized the immune response could be affected as one of targets therapy. Therefore, studied immunosuppressive properties human BM-MSC CMPC their extracellular vesicles (EVs) in...
Abstract Bioactive lipids such as sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) regulate diverse processes including cell proliferation, differentiation, migration. However, their roles in cardiac differentiation cardiomyocyte proliferation have not been explored. Using a 96-well platform for generating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) we found that S1P LPA can independently enhance generation when administered at an early stage of...
Abstract During normal lifespan, the mammalian heart undergoes limited renewal of cardiomyocytes. While exact mechanism for this remains unclear, two possibilities have been proposed: differentiated myocyte replication and progenitor/immature cell differentiation. This study aimed to characterize a population cardiomyocyte precursors in neonatal determine their requirement cardiac development. By tracking expression an embryonic Nkx2.5 enhancer, we identified cardiomyoblasts capable...
Abstract Generating cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) has represented a significant advance in our ability to model cardiac disease. Current differentiation protocols, however, have limited use due their production of heterogenous cell populations, primarily consisting ventricular-like CMs. Here we describe the creation two chamber-specific reporter hiPSC lines by site-directed genomic integration using CRISPR-Cas9 technology. In MYL2-tdTomato reporter,...
Abstract 3D‐scaffold based in vitro human tissue models accelerate disease studies and screening of pharmaceutics while improving the clinical translation findings. Here is reported use induced pluripotent stem cell (hiPSC)‐derived vascular organoid cells as a new source for creation an electrospun polycaprolactone‐bisurea (PCL‐BU) 3D‐scaffold‐based, perfused macrovessel model. A separation protocol developed to obtain monocultures organoid‐derived endothelial (ODECs) mural (ODMCs) from...
Contractility of the adult heart relates to architectural degree sarcomeres in individual cardiomyocytes (CMs) and appears be inversely correlated with ability regenerate. In this study we utilized multiple imaging techniques follow sequence sarcomere disassembly during mitosis resulting cellular or nuclear division a source proliferating human pluripotent stem cell-derived (hiPSC-CMs). We observed that both mono- binuclear hiPSC-CMs give rise mononuclear daughter cells progeny. Within...
Controlled proliferation of cardiomyocytes remains a major limitation in cell biology and one the main underlying hurdles for true modern regenerative medicine. Here, technique is described robust expansion early fetal-derived mouse ventricular on platform usable high-throughput molecular screening, tissue engineering and, potentially, vivo translational experiments. This method provides small-molecule approach to control or differentiation beating through modulation Wnt/β-catenin signaling...