A5085256440- Tissue Engineering and Regenerative Medicine
- Pluripotent Stem Cells Research
- Electrospun Nanofibers in Biomedical Applications
- Protein Tyrosine Phosphatases
- Galectins and Cancer Biology
- 3D Printing in Biomedical Research
- Congenital heart defects research
- Cardiac Fibrosis and Remodeling
- Signaling Pathways in Disease
- Cardiac electrophysiology and arrhythmias
- Cardiac Arrhythmias and Treatments
- Neuroscience and Neural Engineering
- Cardiomyopathy and Myosin Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Cardiac Structural Anomalies and Repair
- Cardiac, Anesthesia and Surgical Outcomes
- Cardiac pacing and defibrillation studies
- Cardiac Valve Diseases and Treatments
- Peptidase Inhibition and Analysis
- CRISPR and Genetic Engineering
- Cardiac Ischemia and Reperfusion
- Neurogenetic and Muscular Disorders Research
- Cardiovascular Syncope and Autonomic Disorders
- Advanced Optical Sensing Technologies
- Renal and related cancers
Universitätsmedizin Göttingen
2019-2025
German Centre for Cardiovascular Research
2020-2025
University of Göttingen
2018-2023
University Medical Center
2022
University Hospital and Clinics
2022
Medizinische Hochschule Hannover
2008-2018
Otto-von-Guericke University Magdeburg
2014-2018
Leipzig University
2018
Columbia University
2017
Vrije Universiteit Amsterdam
2017
To harness the potential of human pluripotent stem cells (hPSCs), an abundant supply their progenies is required. Here, hPSC expansion as matrix-independent aggregates in suspension culture was combined with cardiomyogenic differentiation using chemical Wnt pathway modulators. A multiwell screen scaled up to stirred Erlenmeyer flasks and subsequently tank bioreactors, applying controlled feeding strategies (batch cyclic perfusion). Cardiomyogenesis sensitive GSK3 inhibitor CHIR99021...
Abstract Cardiomyocytes can be implanted to remuscularize the failing heart 1–7 . Challenges include sufficient cardiomyocyte retention for a sustainable therapeutic impact without intolerable side effects, such as arrhythmia and tumour growth. We investigated hypothesis that epicardial engineered muscle (EHM) allografts from induced pluripotent stem cell-derived cardiomyocytes stromal cells structurally functionally chronically limiting effects in rhesus macaques. After confirmation of...
We explored the use of highly purified murine and human pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) to generate functional bioartificial cardiac tissue (BCT) investigated role fibroblasts, ascorbic acid (AA), mechanical stimuli on formation, maturation, functionality. Murine embryonic/induced PSC-derived CMs were genetically enriched three-dimensional CM aggregates, termed bodies (CBs). Addressing critical limitation major loss after single-cell dissociation, non-dissociated CBs...
Alterations in the buffering of intracellular Ca
Stem cell-based cardiac tissue engineering is a promising approach for regenerative therapy of the injured heart. At present, small number stem cell-derived cardiomyocytes that can be obtained using current culture and enrichment techniques represents one key limitations development functional bioartificial (BCT). We have addressed this problem by construction novel bioreactor with features larger systems enables generation in situ monitoring miniaturized BCTs. BCTs were generated from rat...
Hereditary pulmonary alveolar proteinosis (hPAP) caused by granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor α-chain (CSF2RA) deficiency is a rare, life-threatening lung disease characterized accumulation of proteins and phospholipids in the spaces. The functional insufficiency macrophages, which require GM-CSF signaling for terminal differentiation effective degradation phospholipids. Therapeutic options are extremely limited, pathophysiology underlying defective protein...
Abstract Aims Atrial fibrillation (AF) is a commonly occurring arrhythmia after cardiac surgery (postoperative AF, poAF) and associated with poorer outcomes. Considering that reduced atrial contractile function predictor of poAF Ca2+ plays an important role in both excitation–contraction coupling arrhythmogenesis, this study aims to test whether alterations intracellular handling contribute impaired contractility the arrhythmogenic substrate predisposing patients poAF. Methods results Right...
Induced pluripotent stem cells (iPSC) can be differentiated into cardiomyocytes and represent a possible autologous cell source for myocardial repair. We analyzed the engraftment functional effects of murine iPSC-derived (iPSC-CMs) in model infarction.To maximize cardiomyocyte yield purity genetic purification protocol was applied. Murine iPSCs were genetically modified to express Zeocin™ resistance gene under control cardiac-specific α-myosin heavy chain (α-MHC, MYH6) promoter. Thus, CM...
Human pluripotent stem cells (PSCs) open new windows for basic research and regenerative medicine due to their remarkable properties, i.e. ability self-renew indefinitely being pluripotent. There are different, conflicting data related the role of fibroblast growth factor (bFGF) in intracellular signal transduction regulation pluripotency PSCs. Here, we investigated effect bFGF its downstream pathways vs. differentiated human induced (hi) signaling were long-term culture hiPSCs from state...
Abstract Noonan syndrome (NS), the most common among RASopathies, is caused by germline variants in genes encoding components of RAS-MAPK pathway. Distinct variants, including recurrent Ser257Leu substitution RAF1, are associated with severe hypertrophic cardiomyopathy (HCM). Here, we investigated elusive mechanistic link between NS-associated RAF1 S257L and HCM using three-dimensional cardiac bodies bioartificial tissues generated from patient-derived induced pluripotent stem cells (iPSCs)...
Background: Clinical trials of bone marrow cell–based therapies after acute myocardial infarction (MI) have produced mostly neutral results. Treatment with specific cell–derived secreted proteins may provide an alternative biological approach to improving tissue repair and heart function MI. We recently performed a bioinformatic secretome analysis in cells from patients MI discovered poorly characterized protein, EMC10 (endoplasmic reticulum membrane protein complex subunit 10), showing...
The in vitro generation of a bioartificial cardiac construct (CC) represents promising tool for the repair ischemic heart tissue. Several approaches to engineer tissue have been conducted. main drawback these studies is insufficient size resulting clinical applications. focus this study was an artificial three-dimensional (3D), contractile, and suturable myocardial patch by combining gel-based CC with decellularized porcine small intestinal submucosa (SIS), thereby engineering 11 cm2 size....
Atrial fibrillation (AF) is associated with tachycardia-induced cellular electrophysiology alterations which promote AF chronification and treatment resistance. Development of novel antiarrhythmic therapies hampered by the absence scalable experimental human models that reflect AF-associated electrical remodelling. Therefore, we aimed to assess if remodelling can be simulated in atrial-like cardiomyocytes derived from induced pluripotent stem cells presence retinoic acid (iPSC-aCM),...
Cardiac tissue engineering is a promising strategy for regenerative therapies to overcome the shortage of donor organs transplantation. Besides contractile function, stiffness engineered constructs crucial generate transplantable surrogates with sufficient mechanical stability withstand high pressure present in heart. Although several collagen cross-linking techniques have proven be efficient stabilizing biomaterials, they cannot applied cardiac engineering, as cell death occurs treated...
Optical mapping of action potentials or calcium transients in contracting cardiac tissues are challenging because the severe sensitivity measurements to motion. The rely on accurate numerical tracking and analysis fluorescence changes emitted by tissue as it moves, inaccurate no can produce motion artifacts lead imprecise that prohibit data. Recently, was demonstrated motion-tracking -stabilization effectively inhibit artifacts, allowing highly detailed simultaneous electrophysiological...
Abstract Aims Chronic heart failure is becoming increasingly prevalent and still associated with a high mortality rate. Myocardial hypertrophy fibrosis drive cardiac remodelling failure, but they are not sufficiently inhibited by current treatment strategies. Furthermore, despite increasing knowledge on cardiomyocyte intracellular signalling proteins inducing pathological hypertrophy, therapeutic approaches to target these molecules currently unavailable. In this study, we aimed establish...
Abstract Noonan syndrome (NS), the most common among RASopathies, is caused by germline variants in genes encoding components of RAS-MAPK pathway. Distinct variants, including recurrent Ser257Leu substitution RAF1, are associated with severe hypertrophic cardiomyopathy (HCM). Here, we investigated elusive mechanistic link between NS-associated RAF1S257L and HCM using three-dimensional cardiac bodies bioartificial tissues generated from patient-derived induced pluripotent stem cells (iPSCs)...
Aims: Induced pluripotent stem cells (iPSC) represent a suitable autologous cell source for myocardial regeneration and can be differentiated into cardiomyocytes in vitro. We evaluated the potential of murine iPSC-derived (iPSC-CM) to restore tissue improve cardiac function after acute infarction mice. In vitro purification protocols were devised maximize CM yield purity transplantation.
The possibility to generate cardiomyocytes from pluripotent stem cells in vitro has enormous significance for basic research, disease modeling, drug development and heart repair. concept of muscle reconstruction been studied optimized the rat model using primary cardiovascular or xenogeneic cell derived-cardiomyocytes years. However, lack (rPSCs) their derivatives prevented establishment an authentic clinically relevant syngeneic allogeneic regeneration model. In this study, we comparatively...
Even though roughly 90% of all implanted cardiac implantable electronic devices leads can be removed through conventional techniques, presence large vegetations or thrombi, fractured leads, previous failed extraction, long duration from implantation often impede classical transvenous extraction. In these cases, laser-assisted procedures represent a highly successful alternative and have low procedural complication rate with major adverse events in less than 2% cases. Unfortunately, most...