Gregor Fuhrmann

Friedrich-Alexander-Universität Erlangen-Nürnberg

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Marcus Koch

Leibniz-Institute for New Materials

Jean‐Christophe Leroux

ETH Zurich

Kathrin Fuhrmann

Saarland University

Claus‐Michael Lehr

University Medical Center Hamburg-Eppendorf

Adriely Goes

Helmholtz Institute for Pharmaceutical Research Saarland

Alexandra K. Kiemer

Saarland University

Thomas Kuhn

Saarland University

Paola Luciani

University of Bern

Maximilian Richter

Saarland University

Rolf Müller

Helmholtz Centre for Infection Research

Cooperative Institutions

Saarland University

Centre National de la Recherche Scientifique

Inserm

Helmholtz Institute for Pharmaceutical Research Saarland

Friedrich-Alexander-Universität Erlangen-Nürnberg

Helmholtz Centre for Infection Research

Heidelberg University

University Medical Center

Harvard University

Jagiellonian University

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Biobarriers 2018

European Journal of Pharmaceutics and Biopharmaceutics (2020)

Gregor Fuhrmann Brigitta Loretz Nicole Schneider‐Daum Claus‐Michael Lehr

10.1016/j.ejpb.2020.10.014

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Citations (0)

Luteolin protects rat PC 12 and C6 cells against MPP+ induced toxicity via an ERK dependent Keapl-Nrf2-ARE pathway

Christoph-Jan Wruck Malte Christian Claussen Gregor Fuhrmann Lewis H. Romer Anja Schulz

Oxidative stress is central to neuronal damage in neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. In consequence, activation of the cerebral oxidative stress defence is considered as a promising strategy of therapeutic intervention. Here we demonstrate that the flavone luteolin confers neuroprotection against oxidative stress via activation of the nuclear factor erythroid-2-related factor 2 (Nrf2), a transcription factor central to the maintenance of the cellular redox homeostasis. Luteolin protects rat neural PC12 and glial C6 cells from N-methyl-4-phenyl-pyridinium (MPP+) induced toxicity in vitro and effectively activates Nrf2 as shown by ARE-reporter gene assays. This protection critically depends on the activation of Nrf2 since downregulation of Nrf2 by shRNA completely abrogates the protection of luteolin in vitro. Furthermore, the neuroprotective effect of luteolin is abolished by the inhibition of the luteolin-induced ERK1/2-activation. Our results highlight the relevance of Nrf2 for neural cell survival conferred by flavones. In particular, we identified luteolin as a promising lead for the search of orally available, blood brain barrier permeable compounds to support the therapy of neurodegenerative disorders.

Neurotoxicity

10.1007/978-3-211-73574-9_9

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Citations (169)

Extracellular vesicles protect glucuronidase model enzymes during freeze-drying

Scientific Reports (2018)

Julia Frank Maximilian Richter Chiara Rossi Claus‐Michael Lehr Kathrin Fuhrmann

Extracellular vesicles (EVs) are natural nanoparticles that play important roles in intercellular communication and are increasingly studied for biosignalling, pathogenesis and therapy. Nevertheless, little is known about optimal conditions for their transfer and storage, and the potential impact on preserving EV-loaded cargoes. We present the first comprehensive stability assessment of different widely available types of EVs during various storage conditions including -80 °C, 4 °C, room temperature, and freeze-drying (lyophilisation). Lyophilisation of EVs would allow easy handling at room temperature and thus significantly enhance their expanded investigation. A model enzyme, β-glucuronidase, was loaded into different types of EVs derived from mesenchymal stem cells, endothelial cells and cancer cells. Using asymmetric flow field-flow fractionation we proved that the model enzyme is indeed stably encapsulated into EVs. When assessing enzyme activity as indicator for EV stability, and in comparison to liposomes, we show that EVs are intrinsically stable during lyophilisation, an effect further enhanced by cryoprotectants. Our findings provide new insight for exploring lyophilisation as a novel storage modality and we create an important basis for standardised and advanced EV applications in biomedical research.

Glucuronidase

Extracellular Vesicles

Beta-glucuronidase

10.1038/s41598-018-30786-y

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Evaluation of the Storage Stability of Extracellular Vesicles

Journal of Visualized Experiments (2019)

Maximilian Richter Kathrin Fuhrmann Gregor Fuhrmann

Extracellular Vesicles

10.3791/59584-v

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Citations (8)

What's Hot in the Red Journal

The American Journal of Gastroenterology (2010)

Maud Pinier Gregor Fuhrmann Elena F. Verdú Jean‐Christophe Leroux

10.1038/ajg.2010.446

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Expression of the chicken cysteine-rich fibroblast growth factor receptor (CFR) during embryogenesis and retina development

Journal of Neuroscience Research (1996)

N.A. Fayein Mark Head J.C. Jeanny Yves Courtois Gregor Fuhrmann

The expression of the chicken cysteine-rich fibroblast growth factor receptor (CFR) during organogenesis and specifically during retina formation was studied by Northern blotting and a sensitive in situ hybridization. At days 2 and 4 of embryonic development (E2 and E4), CFR mRNA was present in a wide variety of developing organs; it was abundantly expressed in nervous structures, particularly in the retina. The levels of CFR transcripts were high during the proliferation and the subsequent differentiation phases of retinal neurogenesis, reached a maximum around E11 during the onset of the major period of retinal cell death, and then declined progressively. CFR mRNA was not detected at late stages when the final arrangement of retinal cell layers has been established. In prolonged primary cell cultures of chicken embryo retina, CFR expression showed a similar down-regulation to that seen with increasing age in vivo. It was up-regulated either directly or indirectly by its ligands. The CFR expression pattern in the developing retina was complementary to that of two other fibroblast growth factor (FGF) receptors, namely FGF-R1 and FGF-R2. In regard to a progressive increase in the expression of their ligands during retinal development, we suggest that CFR may have a role distinct from that of the tyrosine kinase FGF receptors during retinogenesis. Finally, the comparison of CFR expression with those of the other high affinity receptors indicates a regulation of the FGF function at the receptor level during neural retina development.

Muller glia

10.1002/(sici)1097-4547(19960301)43:5<602::aid-jnr10>3.0.co;2-2

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Citations (14)

Yields and Immunomodulatory Effects of Pneumococcal Membrane Vesicles Differ with the Bacterial Growth Phase

Advanced Healthcare Materials (2021)

Mina Mehanny Tobias Kroniger Marcus Koch Jessica Hoppstädter Dörte Becher

Streptococcus pneumoniae infections are a leading cause of death worldwide. Bacterial membrane vesicles (MVs) are promising vaccine candidates because of the antigenic components of their parent microorganisms. Pneumococcal MVs exhibit low toxicity towards several cell lines, but their clinical translation requires a high yield and strong immunogenic effects without compromising immune cell viability. MVs are isolated during either the stationary phase (24 h) or death phase (48 h), and their yields, immunogenicity and cytotoxicity in human primary macrophages and dendritic cells have been investigated. Death-phase vesicles showed higher yields than stationary-phase vesicles. Both vesicle types displayed acceptable compatibility with primary immune cells and several cell lines. Both vesicle types showed comparable uptake and enhanced release of the inflammatory cytokines, tumor necrosis factor and interleukin-6, from human primary immune cells. Proteomic analysis revealed similarities in vesicular immunogenic proteins such as pneumolysin, pneumococcal surface protein A, and IgA1 protease in both vesicle types, but stationary-phase MVs showed significantly lower autolysin levels than death-phase MVs. Although death-phase vesicles produced higher yields, they lacked superiority to stationary-phase vesicles as vaccine candidates owing to their similar antigenic protein cargo and comparable uptake into primary human immune cells.

Pneumolysin

10.1002/adhm.202101151

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Citations (20)

Celiac Disease: A Challenging Disease for Pharmaceutical Scientists

Pharmaceutical Research (2012)

Simon Matoori Gregor Fuhrmann Jean‐Christophe Leroux

Gluten free

10.1007/s11095-012-0951-x

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Citations (27)

Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy

Advanced Materials (2018)

Gregor Fuhrmann Rona Chandrawati Paresh A. Parmar Timothy J. Keane Stephanie A. Maynard

Abstract Extracellular vesicles (EVs) have recently gained significant attention as important mediators of intercellular communication, potential drug carriers, and disease biomarkers. These natural cell‐derived nanoparticles are postulated to be biocompatible, stable under physiological conditions, and to show reduced immunogenicity as compared to other synthetic nanoparticles. Although initial clinical trials are ongoing, the use of EVs for therapeutic applications may be limited due to undesired off‐target activity and potential “dilution effects” upon systemic administration which may affect their ability to reach their target tissues. To fully exploit their therapeutic potential, EVs are embedded into implantable biomaterials designed to achieve local delivery of therapeutics taking advantage of enzyme prodrug therapy (EPT). In this first application of EVs for an EPT approach, EVs are used as smart carriers for stabilizing enzymes in a hydrogel for local controlled conversion of benign prodrugs to active antiinflammatory compounds. It is shown that the natural EVs' antiinflammatory potential is comparable or superior to synthetic carriers, in particular upon repeated long‐term incubations and in different macrophage models of inflammation. Moreover, density‐dependent color scanning electron microscopy imaging of EVs in a hydrogel is presented herein, an impactful tool for further understanding EVs in biological settings.

Extracellular Vesicles

Biocompatible material

10.1002/adma.201706616

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Citations (94)

Polymer–Enzyme Conjugates for Oral Drug Delivery Applications

CHIMIA International Journal for Chemistry (2013)

Gregor Fuhrmann Marc A. Gauthier Jean‐Christophe Leroux

Conjugate

10.2533/chimia.2013.685

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Citations (1)