A5101548521- Pluripotent Stem Cells Research
- Tissue Engineering and Regenerative Medicine
- CRISPR and Genetic Engineering
- Xenotransplantation and immune response
- Neonatal Respiratory Health Research
- Animal Genetics and Reproduction
- Virus-based gene therapy research
- Electrospun Nanofibers in Biomedical Applications
- Congenital heart defects research
- 3D Printing in Biomedical Research
- Protease and Inhibitor Mechanisms
- Blood Coagulation and Thrombosis Mechanisms
- Renal and related cancers
- Mesenchymal stem cell research
- Cystic Fibrosis Research Advances
- Energy Harvesting in Wireless Networks
- Cardiomyopathy and Myosin Studies
- Biomedical Ethics and Regulation
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Organ Transplantation Techniques and Outcomes
- Cell Adhesion Molecules Research
- Transplantation: Methods and Outcomes
- Cardiac Fibrosis and Remodeling
- Cardiac Ischemia and Reperfusion
German Center for Lung Research
2015-2024
Medizinische Hochschule Hannover
2015-2024
Hannover Re (Germany)
2010-2024
Leibniz Association
2001-2021
de Duve Institute
2021
Luzerner Kantonsspital
2019
Sanden (Japan)
2015
University Hospital of Bern
2013
University of Zurich
2012
Paul Scherrer Institute
2012
Background— The recent breakthrough in the generation of induced pluripotent stem (iPS) cells, which are almost indistinguishable from embryonic (ES) facilitates murine disease– and human patient–specific cell lines. aim this study was to characterize cardiac differentiation potential a iPS clone comparison well-established ES line. Methods Results— With use standard embryoid body–based protocol for cells as well were differentiated 24 days. Although analyzed showed delayed less efficient...
Background— Myocardial infarction leads to cardiac remodeling and development of heart failure. Insufficient myocardial capillary density after has been identified as a critical event in this process, although the underlying mechanisms angiogenesis are mechanistically not well understood. Methods Results— Here, we show that small noncoding RNA microRNA-24 (miR-24) is enriched endothelial cells considerably upregulated ischemia. MiR-24 induces cell apoptosis, abolishes network formation on...
Abstract Organoid models of early tissue development have been produced for the intestine, brain, kidney and other organs, but similar approaches heart lacking. Here we generate complex, highly structured, three-dimensional heart-forming organoids (HFOs) by embedding human pluripotent stem cell aggregates in Matrigel followed directed cardiac differentiation via biphasic WNT pathway modulation with small molecules. HFOs are composed a myocardial layer lined endocardial-like cells surrounded...
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...
The human brain has undergone rapid expansion since humans diverged from other great apes, but the mechanism of this human-specific enlargement is still unknown. Here, we use cerebral organoids derived human, gorilla, and chimpanzee cells to study developmental mechanisms driving evolutionary expansion. We find that neuroepithelial differentiation a protracted process in involving previously unrecognized transition state characterized by change cell shape. Furthermore, show are larger due...
Therapeutic and industrial applications of pluripotent stem cells their derivatives require large cell quantities generated in defined conditions. To this end, we have translated single cell-inoculated suspension cultures human (hPSCs; including induced [hiPS] embryonic [hESC]) to stirred tank bioreactors. These systems that are widely used biopharmaceutical industry allow straightforward scale up detailed online monitoring key process parameters. ensure minimum medium consumption, but...
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...
Evaluation of novel cellular therapies in large-animal models and patients is currently hampered by the lack imaging approaches that allow for long-term monitoring viable transplanted cells. In this study, sodium iodide symporter (NIS) transgene was evaluated as an approach to follow vivo survival, engraftment, distribution human-induced pluripotent stem cell (hiPSC) derivatives a pig model myocardial infarction.Transgenic hiPSC lines stably expressing fluorescent reporter NIS...
AimsInduced pluripotent stem cell (iPSC)-derived cardiovascular progenitor cells represent a suitable autologous source for myocardial regeneration as they have the capability to form and contribute revascularization. As first proof of concept we evaluated potential murine iPSC-derived population, which expresses surface marker foetal liver kinase-1 (Flk-1), restore tissue improve cardiac function after acute infarction (MI) in mice.
Abstract The routine application of human pluripotent stem cells (hPSCs) and their derivatives in biomedicine drug discovery will require the constant supply high-quality by defined processes. Culturing hPSCs as cell-only aggregates (three-dimensional [3D]) suspension has potential to overcome numerous limitations conventional surface-adherent (two-dimensional [2D]) cultivation. Utilizing single-use instrumented stirred-tank bioreactors, we showed that perfusion resulted a more homogeneous...
Abstract The increasing number of severe infections with multi-drug-resistant pathogens worldwide highlights the need for alternative treatment options. Given pivotal role phagocytes and especially alveolar macrophages in pulmonary immunity, we introduce a new, cell-based strategy to target bacterial airway infections. Here show that mass production therapeutic from induced pluripotent stem cells (iPSC) industry-compatible, stirred-tank bioreactors is feasible. Bioreactor-derived...
Human induced pluripotent stem cells (hiPSCs) are capable of unlimited proliferation and can differentiate in vitro to generate derivatives the three primary germ layers. Genetic epigenetic abnormalities have been reported by Wissing colleagues occur during hiPSC derivation, including mobilization engineered LINE-1 (L1) retrotransposons. However, incidence functional impact endogenous retrotransposition hiPSCs yet be established. Here we apply retrotransposon capture sequencing eight lines...
Abstract In vitro differentiation of human pluripotent stem cells (hPSCs) recapitulates early aspects embryogenesis, but the underlying processes are poorly understood and controlled. Here we show that modulating bulk cell density (BCD: number per culture volume) deterministically alters anteroposterior patterning primitive streak (PS)-like priming. The BCD in conjunction with chemical WNT pathway activator CHIR99021 results distinct paracrine microenvironments codifying hPSCs towards...
Aiming at clinical translation, robust directed differentiation of human pluripotent stem cells (hPSCs), preferentially in chemically defined conditions, is a key requirement. Here, feasibility suspension culture based hPSC-cardiomyocyte (hPSC-CM) production low-cost, xeno-free media compatible with good manufacturing practice standards shown. Applying stirred tank bioreactor systems increasing dimensions, our advanced protocol enables routine about 1 million hPSC-CMs/mL, yielding ∼1.3 × 108...
Abstract To harness the full potential of human pluripotent stem cells (hPSCs) we combined instrumented stirred tank bioreactor (STBR) technology with power in silico process modeling to overcome substantial, hPSC-specific hurdles toward their mass production. Perfused suspension culture (3D) matrix-free hPSC aggregates STBRs was applied identify and control process-limiting parameters including pH, dissolved oxygen, glucose lactate levels, obviation osmolality peaks provoked by high density...
In addition to antioxidative and anti-inflammatory properties, activators of the cytoprotective nuclear factor erythroid-2-like-2 (NRF2) signaling pathway have antiviral effects, but underlying mechanisms are incompletely understood. We evaluated ability NRF2 4-octyl itaconate (4OI), bardoxolone methyl (BARD), sulforaphane (SFN), inhibitor exportin-1 (XPO1)-mediated export selinexor (SEL) interfere with influenza virus A/Puerto Rico/8/1934 (H1N1) infection human cells. All compounds reduced...