- Tissue Engineering and Regenerative Medicine
- Cardiac electrophysiology and arrhythmias
- Cardiomyopathy and Myosin Studies
- Electrospun Nanofibers in Biomedical Applications
- Pluripotent Stem Cells Research
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Neuroscience and Neural Engineering
- 3D Printing in Biomedical Research
- Congenital heart defects research
- Cardiovascular Function and Risk Factors
- Heart Failure Treatment and Management
- Cardiac pacing and defibrillation studies
- Cardiac Structural Anomalies and Repair
- Cardiac Ischemia and Reperfusion
- Cardiac Fibrosis and Remodeling
- Viral Infections and Immunology Research
- Cardiovascular Effects of Exercise
- Blood Pressure and Hypertension Studies
- Muscle Physiology and Disorders
- CRISPR and Genetic Engineering
- Phosphodiesterase function and regulation
- Mitochondrial Function and Pathology
- Atrial Fibrillation Management and Outcomes
- Cardiovascular Syncope and Autonomic Disorders
German Centre for Cardiovascular Research
2016-2025
University Medical Center Hamburg-Eppendorf
2016-2025
Universität Hamburg
2016-2025
Institute of Experimental Pharmacology and Toxicology of the Slovak Academy of Sciences
2018-2025
Eppendorf (Belgium)
2024
Arzneimittelkommission der deutschen Ärzteschaft
2023
Martini-Klinik
1995-2022
Eppendorf (Germany)
2011-2021
Nanion (Germany)
2020
Cardiovascular Research Center
2013-2019
Cardiac tissue engineering is an emerging field. The suitability of engineered heart (EHT) for both in vitro and vivo applications will depend on the degree syncytoid formation cardiac myocyte differentiation vitro, contractile function, electrophysiological properties. Here, we demonstrate that myocytes from neonatal rats, when mixed with collagen I matrix factors, cast circular molds, subjected to phasic mechanical stretch, reconstitute ring-shaped EHTs display important hallmarks...
The regulation of cytosolic Ca2+ concentration during excitation-contraction coupling is altered in the failing human heart. Previous studies have focused on disturbances release and reuptake from sarcoplasmic reticulum (SR), whereas functional cardiac Na(+)-Ca2+ exchanger, another important determinant myocyte homeostasis, are lacking for Using a exchanger cDNA recently cloned guinea pig library, we investigated gene expression relation to SR Ca(2+)-ATPase. Expression both genes was...
A method has been developed for culturing cardiac myocytes in a collagen matrix to produce coherently contracting 3-dimensional model heart tissue that allows direct measurement of isometric contractile force. Embryonic chick cardiomyocytes were mixed with solution and allowed gel between two Velcro-coated glass tubes. During culture, the formed spontaneously beating myocyte-populated matrices (CMPMs) anchored at opposite ends Velcro-covered tubes through which they could be attached force...
Tissue engineering may provide advanced in vitro models for drug testing and, combination with recent induced pluripotent stem cell technology, disease modeling, but available techniques are unsuitable higher throughput.Here, we present a new miniaturized and automated method based on engineered heart tissue (EHT).Neonatal rat cells mixed fibrinogen/Matrigel plus thrombin pipetted into rectangular casting molds which two flexible silicone posts positioned from above. Contractile activity is...
A technique is presented that allows neonatal rat cardiac myocytes to form spontaneously and coherently beating 3-dimensional engineered heart tissue (EHT) in vitro, either as a plane biconcaval matrix anchored at both sides on Velcro-coated silicone tubes or ring. Contractile activity was monitored standard organ baths continuously CO(2) incubator for up 18 days (=26 after casting). Long-term measurements showed an increase force between 8 casting stable forces thereafter. At day 10, the...
Human embryonic stem cell (hESC) progenies hold great promise as surrogates for human primary cells, particularly if the latter are not available in case of cardiomyocytes. However, high content experimental platforms lacking that allow function hESC-derived cardiomyocytes to be studied under relatively physiological and standardized conditions. Here we describe a simple robust protocol generation fibrin-based engineered heart tissue (hEHT) 24-well format using an unselected population...
Analyzing contractile force, the most important and best understood function of cardiomyocytes in vivo is not established human induced pluripotent stem cell-derived (hiPSC-CM). This study describes generation 3D, strip-format, force-generating engineered heart tissues (EHT) from hiPSC-CM their physiological pharmacological properties. CM were differentiated hiPSC by a growth factor-based three-stage protocol. EHTs generated analyzed histologically functionally. HiPSC-CM showed...
Spontaneously beating engineered heart tissue (EHT) represents an advanced in vitro model for drug testing and disease modeling, but cardiomyocytes EHTs are less mature generate lower forces than the adult heart. We devised a novel pacing system integrated setup videooptical recording of EHT contractile function over time investigated whether sustained electrical field stimulation improved properties. were generated from neonatal rat cells (rEHT, n=96) or human induced pluripotent stem cell...
Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have enormous potential for the study of human cardiac disorders. However, their physiological immaturity severely limits utility as a model system and adoption drug discovery. Here, we describe maturation media designed to provide oxidative substrates adapted metabolic needs iPSC (hiPSC)-CMs. Compared with conventionally cultured hiPSC-CMs, metabolically matured hiPSC-CMs contract greater force show an increased reliance on...
Generating human skeletal muscle models is instrumental for investigating pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial tissue from pluripotent stem cells, including induced cells (iPSCs) patients with Duchenne, limb-girdle, congenital muscular dystrophies. 3D myogenic differentiation was within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics could be implanted into immunodeficient mice....
Human engineered heart tissue derived from induced pluripotent stem cells improves cardiac function in guinea pigs.
Abstract Aims Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has emerged as a global pandemic. SARS-CoV-2 infection can lead to elevated markers of cardiac injury associated with higher risk mortality. It unclear whether direct cardiomyocytes or mainly secondary lung inflammation. Here, we investigate are permissive for infection. Methods results Two strains infected human induced pluripotent stem cell-derived demonstrated detection...
Sarcomeric gene mutations frequently underlie hypertrophic cardiomyopathy (HCM), a prevalent and complex condition leading to left ventricle thickening heart dysfunction. We evaluated isogenic genome-edited human pluripotent stem cell-cardiomyocytes (hPSC-CM) for their validity model, add clarity to, HCM. CRISPR/Cas9 editing produced 11 variants of the HCM-causing mutation c.C9123T-MYH7 [(p.R453C-β-myosin heavy chain (MHC)] in 3 independent hPSC lines. Isogenic sets were differentiated...