Categories

266846

Research outputs

As an application-oriented research organisation, Fraunhofer aims to conduct highly innovative and solution-oriented research - for the benefit of society and to strengthen the German and European economy.

13954

Projects

Fraunhofer is tackling the current challenges facing industry head on. By pooling their expertise and involving industrial partners at an early stage, the Fraunhofer Institutes involved in the projects aim to turn original scientific ideas into marketable products as quickly as possible.

7703

Researchers

Scientific achievement and practical relevance are not opposites - at Fraunhofer they are mutually dependent. Thanks to the close organisational links between Fraunhofer Institutes and universities, science at Fraunhofer is conducted at an internationally first-class level.

77

Institutes

The Fraunhofer-Gesellschaft is the leading organisation for applied research in Europe. Institutes and research facilities work under its umbrella at various locations throughout Germany.

Recent Additions

  • Publication
    Generation of human induced pluripotent stem cell line MHHi029-A from a male Fabry disease patient carrying c.959A > T mutation
    ( 2024)
    Jahn, C.
    ;
    Juchem, M.
    ;
    Sonnenschein, K.
    ;
    Gietz, A.
    ;
    Buchegger, T.
    ;
    Lachmann, Nico
    ;
    Göhring, G.
    ;
    Behrens, Y.L.
    ;
    ;
    Thum, T.
    ;
    Hoepfner, J.
    Fabry disease (FD) is a rare and inherited monogenetic disease caused by mutations in the X-chromosomal alpha-galactosidase A gene GLA concomitant with accumulation of its substrate globotriaosylceramide (Gb3) and multi-organ symptoms. We derived an induced pluripotent stem cell line, MHHi029-A, from a male FD patient carrying a c.959A > T missense mutation in the GLA gene. The hiPSCs show a normal karyotype, expression of pluripotency markers and trilineage differentiation capacity. Importantly, they present the patient-specific mutation in the GLA gene and are therefore a valuable resource for investigating the FD mechanism and identifying novel therapies.
  • Publication
    Regenerative and progressing lesions in lungs and lung-associated lymph nodes from fourteen 90-day inhalation studies with chemically different particulate materials
    ( 2024)
    Weber, K.
    ;
    Bruer, Gustav
    ;
    Krueger, N.
    ;
    Schuster, T.B.
    ;
    ;
    Rat lungs and lung-associated lymph nodes from 14 inhalation studies with chemically different particulate materials were histopathologically re-evaluated, and the bronchoalveolar lavage fluid (BALF) data and lung burden analyses were compared. All investigated substances caused similar lesions. For most substances, 1 mg/m3 of respirable particulate matter was established as the borderline for adverse morphological changes after the 90-day exposure period, confirmed by the increase in polymorphonuclear neutrophils in BALF. Possible reversibility was demonstrated when recovery groups are included in the study especially allowing the differentiation between regeneration or progressing of inflammatory changes during the recovery period. It was concluded, that the major driver of toxicity is not an intrinsic chemical property of the particle but a particle effect. Concerning classification for specific target organ toxicant (STOT) repeated exposure (RE), this paper highlights that merely comparing the lowest concentration, at which adverse effects were observed, with the Classification Labelling and Packaging (CLP) regulation (EC) no. 1272/2008 guidance values is inappropriate and might lead to a STOT classification under CLP for a large part of the substances discussed in this paper, on the basis of typically mild to moderate findings in rat lung and lung-associated lymph nodes on day 1 after exposure. An in-depth evaluation of the pathologic findings is required and an expert judgement has to be included in the decision on classification and labeling, evaluating the type and severity of effects and comparing these with the classification criteria.
  • Publication
    Monocytes prevent apoptosis of iPSCs and promote differentiation of kidney organoids
    ( 2024)
    Pecksen, E.
    ;
    Tkachuk, S.
    ;
    Schröder, C.
    ;
    Vives Enrich, M.
    ;
    Neog, A.
    ;
    Johnson, C.P.
    ;
    Lachmann, Nico
    ;
    Haller, H.
    ;
    Kiyan, Y.
    Background: Induced pluripotent stem cells (iPSCs)-derived kidney organoids are a promising model for studying disease mechanisms and renal development. Despite several protocols having been developed, further improvements are needed to overcome existing limitations and enable a wider application of this model. One of the approaches to improve the differentiation of renal organoids in vitro is to include in the system cell types important for kidney organogenesis in vivo, such as macrophages. Another approach could be to improve cell survival. Mesodermal lineage differentiation is the common initial step of the reported protocols. The glycogen synthase kinase-3 (GSK-3) activity inhibitor, CHIR99021 (CHIR), is applied to induce mesodermal differentiation. It has been reported that CHIR simultaneously induces iPSCs apoptosis that can compromise cell differentiation. We thought to interfere with CHIR-induced apoptosis of iPSCs using rapamycin. Methods: Differentiation of kidney organoids from human iPSCs was performed. Cell survival and autophagy were analyzed using Cell counting kit 8 (CCK8) kit and Autophagy detection kit. Cells were treated with rapamycin or co-cultured with human monocytes isolated from peripheral blood or iPSCs-macrophages using a transwell co-culture system. Monocyte-derived extracellular vesicles (EVs) were isolated using polyethylene glycol precipitation. Expression of apoptotic markers cleaved Caspase 3, Poly [ADP-ribose] polymerase 1 (PARP-1) and markers of differentiation T-Box Transcription Factor 6 (TBX6), odd-skipped related 1 (OSR1), Nephrin, E-Cadherin, Paired box gene 2 (Pax2) and GATA Binding Protein 3 (Gata3) was assessed by RT-PCR and western blotting. Organoids were imaged by 3D-confocal microscopy. Results: We observed that CHIR induced apoptosis of iPSCs during the initial stage of renal organoid differentiation. Underlying mechanisms implied the accumulation of reactive oxygen species and decreased autophagy. Activation of autophagy by rapamacin and by an indirect co-culture of differentiating iPSCs with iPSCs-macrophages and human peripheral blood monocytes prevented apoptosis induced by CHIR. Furthermore, monocytes (but not rapamycin) strongly promoted expression of renal differentiation markers and organoids development via released extracellular vesicles. Conclusion: Our data suggest that co-culturing of iPSCs with human monocytes strongly improves differentiation of kidney organoids. An underlying mechanism of monocytic action implies, but not limited to, an increased autophagy in CHIR-treated iPSCs. Our findings enhance the utility of kidney organoid models.
  • Publication
    Distribution and suitability of pulmonary surfactants as a vehicle for topically applied antibodies in healthy and SARS-CoV-2 infected rodent lungs
    ( 2024)
    Barlang, L.A.
    ;
    Deimel, I.
    ;
    Mohl, B.P.
    ;
    Blaurock, C.
    ;
    Balkema-Buschmann, A.
    ;
    Weinbender, K.
    ;
    Hess, B.
    ;
    ;
    Merkel, O.M.
    ;
    Popp, A.
    The use of natural pulmonary surfactants (PS) as a drug delivery vehicle for biologics is a more recent therapeutic modality. Herein, we tested different contents of PS regarding their physicochemical properties under stress conditions. The PS content of 12.25 mg/ml (Formulation B) showed desired properties such as an isotonic osmolality ∼300 mOsm/kg and an acceptable viscosity of 8.61 cSt, being lower than in commercially available PS solutions. Formulation B passed the specifications of surface lowering capacities of >80 % total lung capacity and physiologically desired formulation properties were independent of the antibody used in the composition. The identified formulation showed the capability of significantly increasing the oxygen saturation in ex vivo isolated perfused rat lungs, compared to a control and up to 30 min post lavage. In the in vivo setting, we showed that intratracheal administration of a human mAB with and without pulmonary surfactant led to higher amounts of delivered antibody within the alveolar tissue compared to intravenous administration. The antibody with the PS formulation remained longer in the alveolar tissues than the antibody without the PS formulation. Further, SARS-CoV-2 infected Golden Syrian hamsters showed that the intranasally applied antibody reached the site of infection in the alveoli and could be detected in the alveolar region 24 h after the last administration. With this work, we demonstrated that pulmonary surfactants can be used as a pulmonary drug delivery mechanism for antibodies and may subsequently improve the antibody efficacy by increasing the residence time at the desired site of action in the alveolar tissue.

Most viewed

  • Publication
    Bestimmung von in Holzschutzmitteln eingesetzten Wirkstoffen in festen und flüssigen Matrizes
    ( 2000)
    Gunschera, J.
    Infolge der Ausrüstung von Holz mit biozid wirksamen Mitteln zum Schutz vor holzzerstörenden oder -verfärbenden Pilzen und Insekten stellt sich spätestens nach Ablauf der Gebrauchsdauer, aber auch bereits während der Nutzung das Problem des potentiellen Freisetzung der Wirkstoffe in die Umwelt. Dies erfordert Kontrollmechanismen bezüglich des Gehaltes dieser Chemikalien im Holz, aber auch in den zum Schutz des Holzes eingesetzten Produkten. Eine wichtige Voraussetzung für diese Kontrollmechanismen ist das Vorhandensein von Analysenmethoden zur Bestimmung der Gehalte der verwendeten Wirkstoffe in allen relevanten Matrizes. Der Text befaßt sich mit den Besonderheiten der Analytik von Holzschutzmittelwirkstoffen in Holz und insbesondere in den Holzschutzmittelformulierungen.
  • Publication
    On the voltage scaling potential of SONOS non-volatile memory transistors
    ( 2015)
    Ocker, J.
    ;
    Slesazeck, S.
    ;
    Mikolajick, T.
    ;
    Buschbeck, S.
    ;
    Günther, S.
    ;
    Yurchuk, E.
    ;
    Hoffmann, R.
    ;
    Beyer, V.
    With technology scaling of embedded nonvolatile memories, voltage scaling below 12 V is a primary goal to maintain the area efficiency of the memory module. The SONOS technology shows promise as a technology for present and future low voltage memory cells. This paper examines the physics of scaled SONOS gate dielectrics in relation to reducing the operational voltage. In particular, we have examined the influence of tunnel oxide, nitride and top oxide thicknesses. The results are supported by electrical simulation of the SONOS gate dielectric. By properly scaling the dielectric films and utilizing electrical simulation we have determined a limit for scalability of the SONOS technology in terms of operation voltage.