Research

Publications

Below you can find a list of our published research.

128 results

EBioMedicine, Volume 88, 4 1 2023, Pages 104431 Modeling bile duct ischemia and reoxygenation injury in human cholangiocyte organoids for screening of novel cholangio-protective agents. Shi S, Roest HP, van den Bosch TPP, Bijvelds MJC, Boehnert MU, de Jonge J, Dekker SO, de Vries AAF, de Jonge HR, Verstegen MMA, van der Laan LJW

Background: Ischemia of the bile duct is a common feature in liver disease and transplantation, which represents a major cause of morbidity and mortality, especially after liver transplantation. Detailed knowledge of its pathogenesis remains incomplete due to the lack of appropriate in vitro models. Methods: To recapitulate biliary damage induced by ischemia and reperfusion in vitro, human intrahepatic cholangiocyte organoids (ICOs) were grown at low oxygen levels of 1% up to 72 h, followed by r... Abstract

Cardiovascular research, Volume 118, Issue 15, 1 1 2022, Pages e105-e107 Conditional immortalization of human cardiomyocytes for translational in vitro modelling of cardiovascular disease. Harlaar N, Pijnappels DA, de Vries AAF

Abstract

Cited 1 times since 2022 (1.7 per year) source: EuropePMC

Cardiovascular research, Volume 118, Issue 10, 1 1 2022, Pages 2293-2303 Optical ventricular cardioversion by local optogenetic targeting and LED implantation in a cardiomyopathic rat model. Nyns ECA, Jin T, Fontes MS, van den Heuvel T, Portero V, Ramsey C, Bart CI, Zeppenfeld K, Schalij MJ, van Brakel TJ, Ramkisoensing AA, Zhang G, Poelma RH, Ördög B, de Vries AAF, Pijnappels DA

Aims: Ventricular tachyarrhythmias (VTs) are common in the pathologically remodelled heart. These arrhythmias can be lethal, necessitating acute treatment like electrical cardioversion to restore normal rhythm. Recently, it has been proposed that cardioversion may also be realized via optically controlled generation of bioelectricity by the arrhythmic heart itself through optogenetics and therefore without the need of traumatizing high-voltage shocks. However, crucial mechanistic and translation... Abstract

Circulation research, Volume 131, Issue 1, 19 3 2022, Pages 24-41 Sbk2, a Newly Discovered Atrium-Enriched Regulator of Sarcomere Integrity. van Gorp PRR, Zhang J, Liu J, Tsonaka R, Mei H, Dekker SO, Bart CI, De Coster T, Post H, Heck AJR, Schalij MJ, Atsma DE, Pijnappels DA, de Vries AAF

Background: Heart development relies on tight spatiotemporal control of cardiac gene expression. Genes involved in this intricate process have been identified using animals and pluripotent stem cell-based models of cardio(myo)genesis. Recently, the repertoire of cardiomyocyte differentiation models has been expanded with iAM-1, a monoclonal line of conditionally immortalized neonatal rat atrial myocytes (NRAMs), which allows toggling between proliferative and differentiated (ie, excitable and co... Abstract

Cited 14 times since 2022 (15.8 per year) source: EuropePMC

Cell metabolism, Volume 34, Issue 4, 18 3 2022, Pages 533-548.e12 Ejection of damaged mitochondria and their removal by macrophages ensure efficient thermogenesis in brown adipose tissue. Rosina M, Ceci V, Turchi R, Chuan L, Borcherding N, Sciarretta F, Sánchez-Díaz M, Tortolici F, Karlinsey K, Chiurchiù V, Fuoco C, Giwa R, Field RL, Audano M, Arena S, Palma A, Riccio F, Shamsi F, Renzone G, Verri M, Crescenzi A, Rizza S, Faienza F, Filomeni G, Kooijman S, Rufini S, de Vries AAF, Scaloni A, Mitro N, Tseng YH, Hidalgo A, Zhou B, Brestoff JR, Aquilano K, Lettieri-Barbato D

Recent findings have demonstrated that mitochondria can be transferred between cells to control metabolic homeostasis. Although the mitochondria of brown adipocytes comprise a large component of the cell volume and undergo reorganization to sustain thermogenesis, it remains unclear whether an intercellular mitochondrial transfer occurs in brown adipose tissue (BAT) and regulates adaptive thermogenesis. Herein, we demonstrated that thermogenically stressed brown adipocytes release extracellular v... Abstract

Cited 5 times since 2022 (4.6 per year) source: EuropePMC

Nature biomedical engineering, Volume 6, Issue 4, 6 1 2022, Pages 389-402 Conditional immortalization of human atrial myocytes for the generation of in vitro models of atrial fibrillation. Harlaar N, Dekker SO, Zhang J, Snabel RR, Veldkamp MW, Verkerk AO, Fabres CC, Schwach V, Lerink LJS, Rivaud MR, Mulder AA, Corver WE, Goumans MJTH, Dobrev D, Klautz RJM, Schalij MJ, Veenstra GJC, Passier R, van Brakel TJ, Pijnappels DA, de Vries AAF

The lack of a scalable and robust source of well-differentiated human atrial myocytes constrains the development of in vitro models of atrial fibrillation (AF). Here we show that fully functional atrial myocytes can be generated and expanded one-quadrillion-fold via a conditional cell-immortalization method relying on lentiviral vectors and the doxycycline-controlled expression of a recombinant viral oncogene in human foetal atrial myocytes, and that the immortalized cells can be used to generat... Abstract

Circulation. Arrhythmia and electrophysiology, Volume 15, Issue 1, 23 4 2021, Pages e009886 Ultrasound-Guided Optogenetic Gene Delivery for Shock-Free Ventricular Rhythm Restoration. Nyns ECA, Jin T, Bart CI, Bax WH, Zhang G, Poelma RH, de Vries AAF, Pijnappels DA

Abstract

Cited 1 times since 2021 (0.7 per year) source: EuropePMC

Frontiers in physiology, Volume 12, 3 1 2021, Pages 692496 Fast Optical Investigation of Cardiac Electrophysiology by Parallel Detection in Multiwell Plates. Credi C, Balducci V, Munagala U, Cianca C, Bigiarini S, de Vries AAF, Loew LM, Pavone FS, Cerbai E, Sartiani L, Sacconi L

Current techniques for fast characterization of cardiac electrophysiology employ optical technologies to control and monitor action potential features of single cells or cellular monolayers placed in multiwell plates. High-speed investigation capacities are commonly achieved by serially analyzing well after well employing fully automated fluorescence microscopes. Here, we describe an alternative cost-effective optical approach (MULTIPLE) that exploits high-power LED arrays to globally illuminate... Abstract

Cited 5 times since 2021 (3.5 per year) source: EuropePMC

Stem cell reports, Volume 16, Issue 9, 2 1 2021, Pages 2159-2168 Engineered 3D vessel-on-chip using hiPSC-derived endothelial- and vascular smooth muscle cells. Vila Cuenca M, Cochrane A, van den Hil FE, de Vries AAF, Lesnik Oberstein SAJ, Mummery CL, Orlova VV

Crosstalk between endothelial cells (ECs) and pericytes or vascular smooth muscle cells (VSMCs) is essential for the proper functioning of blood vessels. This balance is disrupted in several vascular diseases but there are few experimental models which recapitulate this vascular cell dialogue in humans. Here, we developed a robust multi-cell type 3D vessel-on-chip (VoC) model based entirely on human induced pluripotent stem cells (hiPSCs). Within a fibrin hydrogel microenvironment, the hiPSC-der... Abstract

Frontiers in physiology, Volume 12, 23 4 2021, Pages 710020 The Effects of Repetitive Use and Pathological Remodeling on Channelrhodopsin Function in Cardiomyocytes. Ördög B, Teplenin A, De Coster T, Bart CI, Dekker SO, Zhang J, Ypey DL, de Vries AAF, Pijnappels DA

Aim: Channelrhodopsins (ChRs) are a large family of light-gated ion channels with distinct properties, which is of great importance in the selection of a ChR variant for a given application. However, data to guide such selection for cardiac optogenetic applications are lacking. Therefore, we investigated the functioning of different ChR variants in normal and pathological hypertrophic cardiomyocytes subjected to various illumination protocols. Methods and Results: Isolated neonatal rat ventricul... Abstract

Cited 1 times since 2021 (0.7 per year) source: EuropePMC

Cells, Volume 10, Issue 8, 12 2 2021, Pages 2064 Generation, Characterization, and Application of Inducible Proliferative Adult Human Epicardium-Derived Cells. Ge Y, Smits AM, Liu J, Zhang J, van Brakel TJ, Goumans MJTH, Jongbloed MRM, de Vries AAF

In recent decades, the great potential of human epicardium-derived cells (EPDCs) as an endogenous cell source for cardiac regeneration has been recognized. The limited availability and low proliferation capacity of primary human EPDCs and phenotypic differences between EPDCs obtained from different individuals hampers their reproducible use for experimental studies. To generate and characterize inducible proliferative adult human EPDCs for use in fundamental and applied research. Inducible proli... Abstract

Cited 4 times since 2020 (1.9 per year) source: EuropePMC

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, Volume 103, 14 2 2020, Pages 300-304 A high-throughput drug screening strategy against coronaviruses. Liu J, Li K, Cheng L, Shao J, Yang S, Zhang W, Zhou G, de Vries AAF, Yu Z

The emergence and re-emergence of coronaviruses (CoV) continually cause circulating epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. The resultant disease, coronavirus disease 2019 (COVID-19), has rapidly developed into a worldwide pandemic, leading to severe health and economic burdens. Although the recently announced vaccines against COVID-19 has rekindled hope, there is still a major challenge to urgently meet the global need for rapid trea... Abstract

Cited 9 times since 2020 (3.5 per year) source: EuropePMC

Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation, Volume 28, Issue 7-8, 1 1 2020, Pages 396-405 Renin-angiotensin system inhibition in COVID-19 patients. de Vries AAF

Angiotensin-converting enzyme (ACE) inhibitors (ACEIs) and angiotensin II type‑1 receptor blockers (ARBs) are among the most widely prescribed drugs for the treatment of arterial hypertension, heart failure and chronic kidney disease. A number of studies, mainly in animals and not involving the lungs, have indicated that these drugs can increase expression of angiotensin-converting enzyme 2 (ACE2). ACE2 is the cell entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), t... Abstract

Cited 5 times since 2020 (1.9 per year) source: EuropePMC

Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation, Volume 28, Issue 7-8, 1 1 2020, Pages 366-383 SARS-CoV-2/COVID-19: a primer for cardiologists. de Vries AAF

In the late autumn of 2019, a new potentially lethal human coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The pandemic spread of this zoonotic virus has created a global health emergency and an unprecedented socioeconomic crisis. The severity of coronavirus disease 2019 (COVID-19), the illness caused by SARS-CoV‑2, is highly variable. Most patients (~85%) develop no or mild symptoms, while others become seriously ill, some succumbing... Abstract

Cited 2 times since 2020 (0.8 per year) source: EuropePMC

eLife, Volume 9, 8 2 2020, Pages e55921 Self-restoration of cardiac excitation rhythm by anti-arrhythmic ion channel gating. Majumder R, De Coster T, Kudryashova N, Verkerk AO, Kazbanov IV, Ördög B, Harlaar N, Wilders R, de Vries AA, Ypey DL, Panfilov AV, Pijnappels DA

Homeostatic regulation protects organisms against hazardous physiological changes. However, such regulation is limited in certain organs and associated biological processes. For example, the heart fails to self-restore its normal electrical activity once disturbed, as with sustained arrhythmias. Here we present proof-of-concept of a biological self-restoring system that allows automatic detection and correction of such abnormal excitation rhythms. For the heart, its realization involves the inte... Abstract

Cited 140 times since 2020 (51.9 per year) source: EuropePMC

Cell stem cell, Volume 26, Issue 6, 26 4 2020, Pages 862-879.e11 Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease. Giacomelli E, Meraviglia V, Campostrini G, Cochrane A, Cao X, van Helden RWJ, Krotenberg Garcia A, Mircea M, Kostidis S, Davis RP, van Meer BJ, Jost CR, Koster AJ, Mei H, Míguez DG, Mulder AA, Ledesma-Terrón M, Pompilio G, Sala L, Salvatori DCF, Slieker RC, Sommariva E, de Vries AAF, Giera M, Semrau S, Tertoolen LGJ, Orlova VV, Bellin M, Mummery CL

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 cardiac endothelial cells also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs in MTs with CFs showed improved sarcomeric structures with T-tubules, enhanced c... Abstract

Cited 16 times since 2020 (5.6 per year) source: EuropePMC

Circulation research, Volume 127, Issue 2, 6 1 2020, Pages 229-243 Identification of Functional Variant Enhancers Associated With Atrial Fibrillation. van Ouwerkerk AF, Bosada FM, Liu J, Zhang J, van Duijvenboden K, Chaffin M, Tucker NR, Pijnappels D, Ellinor PT, Barnett P, de Vries AAF, Christoffels VM

Rationale: Genome-wide association studies have identified a large number of common variants (single-nucleotide polymorphisms) associated with atrial fibrillation (AF). These variants are located mainly in noncoding regions of the genome and likely include variants that modulate the function of transcriptional regulatory elements (REs) such as enhancers. However, the actual REs modulated by variants and the target genes of such REs remain to be identified. Thus, the biological mechanisms by whic... Abstract

Cited 12 times since 2020 (4.2 per year) source: EuropePMC

Frontiers in cardiovascular medicine, Volume 7, 31 5 2020, Pages 43 Multicellular In vitro Models of Cardiac Arrhythmias: Focus on Atrial Fibrillation. van Gorp PRR, Trines SA, Pijnappels DA, de Vries AAF

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice with a large socioeconomic impact due to its associated morbidity, mortality, reduction in quality of life and health care costs. Currently, antiarrhythmic drug therapy is the first line of treatment for most symptomatic AF patients, despite its limited efficacy, the risk of inducing potentially life-threating ventricular tachyarrhythmias as well as other side effects. Alternative, in-hospital treatment modalitie... Abstract

Cited 1 times since 2020 (0.3 per year) source: EuropePMC

Journal of applied physiology (Bethesda, Md. : 1985), Volume 128, Issue 3, 30 5 2020, Pages 545-553 The proarrhythmic features of pathological cardiac hypertrophy in neonatal rat ventricular cardiomyocyte cultures. Neshati Z, Schalij MJ, de Vries AAF

Different factors may trigger arrhythmias in diseased hearts, including fibrosis, cardiomyocyte hypertrophy, hypoxia, and inflammation. This makes it difficult to establish the relative contribution of each of them to the occurrence of arrhythmias. Accordingly, in this study, we used an in vitro model of pathological cardiac hypertrophy (PCH) to investigate its proarrhythmic features and the underlying mechanisms independent of fibrosis or other PCH-related processes. Neonatal rat ventricular ca... Abstract

Cited 27 times since 2019 (8.2 per year) source: EuropePMC

Nature communications, Volume 10, Issue 1, 18 3 2019, Pages 4755 Identification of atrial fibrillation associated genes and functional non-coding variants. van Ouwerkerk AF, Bosada FM, van Duijvenboden K, Hill MC, Montefiori LE, Scholman KT, Liu J, de Vries AAF, Boukens BJ, Ellinor PT, Goumans MJTH, Efimov IR, Nobrega MA, Barnett P, Martin JF, Christoffels VM

Disease-associated genetic variants that lie in non-coding regions found by genome-wide association studies are thought to alter the functionality of transcription regulatory elements and target gene expression. To uncover causal genetic variants, variant regulatory elements and their target genes, here we cross-reference human transcriptomic, epigenomic and chromatin conformation datasets. Of 104 genetic variant regions associated with atrial fibrillation candidate target genes are prioritized.... Abstract