Fraunhofer Institute for Toxicology and Experimental Medicine
Fraunhofer Institute for Toxicology and Experimental Medicine

Preclinical Research: Disease Models at Fraunhofer ITEM

© Fraunhofer ITEM, Fabian Röpken

Experts for respiratory diseases

 

Test the safety and efficacy of your therapeutics, including small molecules, cell therapies, antibodies, and RNA therapies.

 

Our human, disease-relevant models for respiratory diseases

 
 

Diseases: Relevant publications

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Fibrosis

Srivastava M, Steinwede K, Kiviranta R, Morko J, Hoymann HG, Laenger F, Buehling F, Welte T, Maus U. Overexpression of cathepsin K in mice decreases collagen deposition and lung resistance in response to bleomycin-induced pulmonary fibrosis. Respiratory Research 9 (2008): 54.

Ueberberg B, Janze AK, Steinwede K, Maus R, Mägel L, Hoymann HG, Braun A, Länger F, Jonigk D, Gauldie J, Welte T, Maus UA. Bacterial infection triggers exacerbation of established pulmonary fibrosis in mice: impact on lung protective immunity. Am J Respir Crit Care Med 185 (2012): A3921.

Hoymann, HG, Ernst H, Creutzenberg O, Schaudien D, Müller M, Knudson L, Braun A. Invasive but repetitive lung function measurements in a rodent model of pulmonary fibrosis. Am J Respir Crit Care Med 189 (2014): A1952.

Hoymann, HG, Schaudien D, Hansen T, Müller M, Braun A. Comparison of fibrotic and emphysematous alterations in the lungs of bleomycin-treated rats and hamsters. Am J Respir Crit Care Med 191 (2015): A3454.

Hoymann HG, Schaudien D, Hansen T, Niehof M, Braun A. Functional, histological and biochemical endpoints for assessing antifibrotic efficacy in a rat model of pulmonary fibrosis . Am J Respir Crit Care Med 2016 (in press).

Switalla S, Lauenstein L, Prenzler F, Knothe S, Förster C, Fieguth HG, Pfennig O, Schaummann F, Martin C, Guzman CA, Ebensen T, Müller M, Hohlfeld JM, Krug N, Braun A, Sewald K. Natural innate cytokine response to immunomodulators and adjuvants in human precision-cut lung slices. Toxicol Appl Pharmacol 246 (2010): 107-115.

Switalla S, Knebel J, Ritter D, Krug N, Braun A, Sewald K. Effects of acute in vitro exposure of murine precision-cut lung slices to gaseous nitrogen dioxide and ozone in an air-liquid interface (ALI) culture. Toxicol Lett 196 (2010): 117-124.

Seehase S, Schlepütz M, Switalla S, Mätz-Rensing K, Kaup FJ, Zöller M, Schlumbohm C, Fuchs E, Lauenstein HD, Winkler C, Kuehl AR, Uhlig S, Braun A, Sewald K, Martin C. Bronchoconstriction in nonhuman primates: a species comparison. J Appl Physiol 111 (2011): 791-798.

Seehase S, Lauenstein HD, Schlumbohm C, Switalla S, Neuhaus V, Förster C, Fuchs E, Kaup FJ, Zöller M, Braun A, Sewald K, Knauf S. LPS-induced lung inflammation in marmoset monkeys – an acute model for anti-inflammatory drug testing. PLoS ONE August 28, 2012, doi: 10.1371/journal.pone.0043709.

Lauenstein L, Switalla S, Prenzler F, Seehase S, Pfennig O, Förster C, Fieguth H, Braun A, Sewald K. Assessment of immunotoxicity induced by chemicals in human precision-cut lung slices (PCLS). Toxicol In Vitro 28 (2014): 588-599.

Hess A, Wang-Lauenstein L, Braun A, Kolle SN, Landsiedel R, Liebsch M, Ma-Hock L, Pirow R, Schneider X, Steinfath M, Vogel S, Martin C, Sewald K. Prevalidation of the ex-vivo model PCLS for prediction of respiratory toxicity, Toxicol In Vitro 32 (2016): 347-61.

Infection

Abdin, S. M., Paasch, D., Lachmann, N. (2024). CAR macrophages on a fast track to solid tumor therapy. Nature Immunology 25(1): 11-12. doi: 10.1038/s41590-023-01696-7 https://www.nature.com/articles/s41590-023-01696-7

Chiyyeadu, A., Asgedom, G., Bruhn, M., Rocha, C., Schlegel, T. U., Neumann, T., Galla, M., Barbosa, P. V., Hoffmann, M., Ehrhardt, K., Ha, T. C., Morgan, M., Schoeder, C. T., Pohlmann, S., Kalinke, U., Schambach, A. (2024). A tetravalent bispecific antibody outperforms the combination of its parental antibodies and neutralizes diverse SARS-CoV-2 variants. Clinical Immunology [Epub ahead of print]: 109902. doi: 10.1016/j.clim.2024.109902 https://www.sciencedirect.com/science/article/pii/S1521661624000135?via%3Dihub  - Open Access

Diesendorf, V., Roll, V., Geiger, N., Fähr, S., Obernolte, H., Sewald, K., Bodem, J. (2023). Drug-induced phospholipidosis is not correlated with the inhibition of SARS-CoV-2 - inhibition of SARS-CoV-2 is cell line-specific. Frontiers in Cellular and Infection Microbiology 13. doi: 10.3389/fcimb.2023.1100028 https://www.frontiersin.org/articles/10.3389/fcimb.2023.1100028/full  - Open Access

Fleischauer, J., Bastone, A. L., Selich, A., John-Neek, P., Weisskoeppel, L., Schaudien, D., Schambach, A., Rothe, M. (2023). TGFβ Inhibitor A83-01 Enhances Murine HSPC Expansion for Gene Therapy. Cells 12(15): 1978. doi: 10.3390/cells12151978 https://www.mdpi.com/2073-4409/12/15/1978  - Open Access

Hammad, R., Alzubi, J., Rhiel, M., Chmielewski, K. O., Mosti, L., Rositzka, J., Heugel, M., Lawrenz, J., Pennucci, V., Glaser, B., Fischer, J., Schambach, A., Moritz, T., Lachmann, N., Cornu, T. I., Mussolino, C., Schafer, R., Cathomen, T. (2024). CRISPR-Cas12a for Highly Efficient and Marker-Free Targeted Integration in Human Pluripotent Stem Cells. Int J Mol Sci 25(2): 985. doi: 10.3390/ijms25020985 https://www.mdpi.com/1422-0067/25/2/985 - Open Access

Hetzel, M., Gensch, I., Ackermann, M., Lachmann, N. (2024). Adaptation of Human iPSC-Derived Macrophages Toward an Alveolar Macrophage-Like Phenotype Post-Intra-Pulmonary Transfer into Murine Models. Methods in Molecular Biology 2713: 463-479. doi: 10.1007/978-1-0716-3437-0_31 https://link.springer.com/protocol/10.1007/978-1-0716-3437-0_31

Hilbold, E., Bär, C., Thum, T. (2023). COVID-19: Insights into long-term manifestations and lockdown impacts. J Sport Health Sci [Epub ahead of print]. doi: 10.1016/j.jshs.2023.02.006 https://www.sciencedirect.com/science/article/pii/S2095254623000194?via%3Dihub - Open Access

Hou, R., Ye, G., Cheng, X., Shaw, D. E., Bakke, P. S., Caruso, M., Dahlen, B., Dahlen, S. E., Fowler, S. J., Horvath, I., Howarth, P., Krug, N., Montuschi, P., Sanak, M., Sandstrom, T., Auffray, C., De Meulder, B., Sousa, A. R., Adcock, I. M., Fan Chung, K., Sterk, P. J., Skipp, P. J., Schofield, J., Djukanovic, R., U. Biopred Study Group (2023). The role of inflammation in anxiety and depression in the European U-BIOPRED asthma cohorts. Brain, Behavior, and Immunity 111: 249-258. doi: 10.1016/j.bbi.2023.04.011 https://www.sciencedirect.com/science/article/pii/S0889159123001095?via%3Dihub  - Open Access

Nowak, J., Bentele, M., Kutle, I., Zimmermann, K., Luhmann, J. L., Steinemann, D., Kloess, S., Koehl, U., Rossberg, W., Ahmed, A., Schaudien, D., Neubert, L., Kamp, J. C., Kuehnel, M. P., Warnecke, A., Schambach, A., Morgan, M. (2023). CAR-NK Cells Targeting HER1 (EGFR) Show Efficient Anti-Tumor Activity against Head and Neck Squamous Cell Carcinoma (HNSCC). Cancers 15(12): 3169. doi: 10.3390/cancers15123169 https://www.mdpi.com/2072-6694/15/12/3169  - Open Access

Rudolph, D., Redinger, N., Schwarz, K., Li, F., Hadrich, G., Cohrs, M., Dailey, L. A., Schaible, U. E., Feldmann, C. (2023). Amorphous Drug Nanoparticles for Inhalation Therapy of Multidrug-Resistant Tuberculosis. ACS Nano 17(10): 9478-9486. doi: 10.1021/acsnano.3c01664 https://pubs.acs.org/doi/10.1021/acsnano.3c01664

Sansonetti, M., Al Soodi, B., Thum, T., Jung, M. (2024). Macrophage-based therapeutic approaches for cardiovascular diseases. Basic Research in Cardiology [Epub ahead of print]. doi: 10.1007/s00395-023-01027-9 https://link.springer.com/article/10.1007/s00395-023-01027-9 - Review

Sommer, C., Reamon-Buettner, S. M., Niehof, M., Hildebrand, C. B., Braun, A., Sewald, K., Dehmel, S., Brandenberger, C. (2024). Age-dependent inflammatory response is altered in an ex vivo model of bacterial pneumonia. Respiratory Research 25(1): 15. doi: 10.1186/s12931-023-02609-w https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-023-02609-w - Open Access

Asthma

Hoymann HG and Heinrich U. Measurement of lung function in rodents in vivo. In: Methods in pulmonary research. Uhlig S and Taylor AE (eds.). Birkhäuser Verlag, Basel 1998, 1-28.

Glaab T, Hoymann HG, Hohlfeld J, Korolewitz R, Hecht M, Alarie Y, Tschernig T, Braun A, Krug N, and Fabel H. Noninvasive measurement of midexpiratory flow indicates bronchoconstriction in allergic rats. Journal of Applied Physiology 93 (2002): 1208.

Glaab T, Hoymann HG, Hecht M, Korolewitz R, Tschernig T, Hohlfeld J, Krug N, and Braun A. Effect of anti-nerve growth factor on early and late airway responses in allergic rats. Allergy 58 (2003): 900-904.

Duechs MJ, Hahn C, Benediktus E, Werner-Klein M, Braun A, Hoymann HG, Gantner F, Erb KJ. TLR agonist mediated suppression of allergic responses is associated with increased innate inflammation in the airways. Pulm Pharmacol Ther 24 (2011): 203-214.

Rückert R, Brandt K, Braun A, Hoymann HG, Herz U, Budagian V, Dürkop H, Renz H, Bulfone-Paus S. Blocking IL-15 prevents the induction of allergen-specific T-cells and allergic inflammation in vivo. J Immunol 174 (2005), No. 9: 5507-5515.

Weigt H et al. Efficacy of macrophage-activating lipopeptide-2 combined with interferon-γ in a murine asthma model. Am J Respir Crit Care Med 172 (2005): 566–572.

Hoymann HG. Appraisal of state-of-the-art: invasive and noninvasive lung function measurements in rodents. Journal of Pharmacological and Toxicological Methods 55 (2007), No. 1: 16-26.

Winkler C, Bahlmann O, Viereck J, Knudsen L, Wedekind D, Hoymann HG, Madsen J, Thum T, Hohlfeld JM, Ochs M. Impact of a Met(11)Thr single nucleotide polymorphism of surfactant protein D on allergic airway inflammation in a murine asthma model. Exp Lung Res 40 (2014), No. 4: 154-163.

COPD

Curths C, Wichmann J, Dunker S, Windt H, Hoymann HG, Lauenstein HD, Hohlfeld J, Becker T, Kaup FJ, Braun A, and Knauf S. Airway hyper-responsiveness in lipopolysaccharide-challenged common marmosets (Callithrix jacchus). Clin Sci (Lond). 126 (2014), No. 2: 155-162.

Seehase S, Schleputz M, Switalla S, Matz-Rensing K, Kaup FJ, Zoller M, Schlumbohm C, Fuchs E, Lauenstein HD, Winkler C, Kuehl AR, Uhlig S, Braun A, Sewald K, and Martin C. Bronchoconstriction in nonhuman primates: a species comparison. J Appl Physiol. 111 (2011), No. 3: 791-798.

Seehase S, Lauenstein HD, Schlumbohm C, Switalla S, Neuhaus V, Forster C, Fieguth HG, Pfennig O, Fuchs E, Kaup FJ, Bleyer M, Hohlfeld JM, Braun A, Sewald K, and Knauf S. LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing. PLoS One. 7 (2012), No. 8: e43709.

Switalla S, Lauenstein L, Prenzler F, Knothe S, Förster C, Fieguth HG, Pfennig O, Schaummann F, Martin C, Guzman CA, Ebensen T, Müller M, Hohlfeld JM, Krug N, Braun A, Sewald K. Natural innate cytokine response to immunomodulators and adjuvants in human precision-cut lung slices. Toxicol Appl Pharmacol 246 (2010): 107-115.

Switalla S, Knebel J, Ritter D, Krug N, Braun A, Sewald K. Effects of acute in vitro exposure of murine precision-cut lung slices to gaseous nitrogen dioxide and ozone in an air-liquid interface (ALI) culture. Toxicol Lett 196 (2010): 117-124.

Seehase S, Schlepütz M, Switalla S, Mätz-Rensing M, Kaup FJ, Zöller M, Schlumbohm C, Fuchs E, Lauenstein HD, Winkler C, Kuehl AR, Uhlig S, Braun A, Sewald K, Martin C. Bronchoconstriction in nonhuman primates: a species comparison. J Appl Physiol 111 (2011): 791-798.

Seehase S, Lauenstein HD, Schlumbohm C, Switalla S, Neuhaus V, Förster C, Fuchs E, Kaup FJ, Zöller M, Braun A, Sewald K, Knauf S. LPS-induced lung inflammation in marmoset monkeys – an acute model for anti-inflammatory drug testing. PLoS ONE August 28, 2012, doi: 10.1371/journal.pone.0043709

Lauenstein L, Switalla S, Prenzler F, Seehase S, Pfennig O, Förster C, Fieguth H, Braun A, Sewald K. Assessment of immunotoxicity induced by chemicals in human precision-cut lung slices (PCLS). Toxicol In Vitro 28 (2014): 588-599.

Hess A, Wang-Lauenstein L, Braun A, Kolle SN, Landsiedel R, Liebsch M, Ma-Hock L, Pirow R, Schneider X, Steinfath M, Vogel S, Martin C, Sewald K. Prevalidation of the ex-vivo model PCLS for prediction of respiratory toxicity. Toxicol In Vitro 32 (2016): 347-61.

Sewald K and Braun A. PCLS: From learning about ‘in vivo’ to reduction and replacement. In: Progress towards novel testing strategies for in vitro assessment of allergens. Roggen EL, Weltzien HU, Hermans H (eds.). Kerala/India: Research Signpost, 2011, pp. 13-34.

Sewald K and Braun A. Precision-cut tissue slices in pharmacology and toxicology. Xenobiotica 43 (2013): 84-97.

Cancer

  • Abdin, S. M., Paasch, D., Lachmann, N. (2024). CAR macrophages on a fast track to solid tumor therapy. Nature Immunology 25(1): 11-12. doi: 10.1038/s41590-023-01696-7 https://www.nature.com/articles/s41590-023-01696-7
  • Adler, O., Zait, Y., Cohen, N., Blazquez, R., Doron, H., Monteran, L., Scharff, Y., Shami, T., Mundhe, D., Glehr, G., Kanner, A. A., Horn, S., Yahalom, V., Haferkamp, S., Hutchinson, J. A., Bleckmann, A., Nahary, L., Benhar, I., Katz, S. Y., Pukrop, T., Erez, N. (2023). Reciprocal interactions between innate immune cells and astrocytes facilitate neuroinflammation and brain metastasis via lipocalin-2. Nat Cancer [Epub ahead of print]. doi: 10.1038/s43018-023-00519-w https://www.nature.com/articles/s43018-023-00519-w
  • Agudo, J., Aguirre-Ghiso, J. A., Bhatia, M., Chodosh, L. A., Correia, A. L., Klein, C. A. (2024). Targeting cancer cell dormancy. Nature Reviews: Cancer 24: 97–104. doi: 10.1038/s41568-023-00642-x https://www.nature.com/articles/s41568-023-00642-x
  • Asami, M., Lam, B. Y. H., Hoffmann, M., Suzuki, T., Lu, X., Yoshida, N., Ma, M. K., Rainbow, K., Guzvic, M., VerMilyea, M. D., Yeo, G. S. H., Klein, C. A., Perry, A. C. F. (2023). A program of successive gene expression in mouse one-cell embryos. Cell Rep 42(2): 112023. doi: 10.1016/j.celrep.2023.112023 https://www.sciencedirect.com/science/article/pii/S2211124723000347?via%3Dihub - Open Access 28 February 2023
  • Feliciello, G., Czyz, Z. T., Polzer, B. M. (2024). Array-Based Comparative Genomic Hybridization for the Detection of Copy Number Alterations in Single Cells. Methods in Molecular Biology 2752: 167-187. doi: 10.1007/978-1-0716-3621-3_11 https://link.springer.com/protocol/10.1007/978-1-0716-3621-3_11
  • Franken, A., Kraemer, A., Sicking, A., Watolla, M., Rivandi, M., Yang, L., Warfsmann, J., Polzer, B. M., Friedl, T. W. P., Meier-Stiegen, F., Stoecklein, N. H., Dayan, D., Riethdorf, S., Mueller, V., Pantel, K., Koch, A., Hartkopf, A. D., Krawczyk, N., Ruckhaeberle, E., Niederacher, D., Fehm, T., Neubauer, H. (2023). Comparative analysis of EpCAM high-expressing and low-expressing circulating tumour cells with regard to their clonal relationship and clinical value. British Journal of Cancer [Epub ahead of print]. doi: 10.1038/s41416-023-02179-0 https://www.nature.com/articles/s41416-023-02179-0 - Open Access 23 februar 2023
  • Hücker, S. M., Kirsch, S. (2024). Single Cell Micro RNA Sequencing Library Preparation. Methods in Molecular Biology 2752: 189-199. doi: 10.1007/978-1-0716-3621-3_12 https://link.springer.com/protocol/10.1007/978-1-0716-3621-3_12
  • Klusa, D., Lohaus, F., Franken, A., Baumbach, M., Cojoc, M., Dowling, P., Linge, A., Offermann, A., Lock, S., Husman, D., Rivandi, M., Polzer, B., Freytag, V., Lange, T., Neubauer, H., Kucken, M., Perner, S., Holscher, T., Dubrovska, A., Krause, M., Kurth, I., Baumann, M., Peitzsch, C. (2023). Dynamics of CXCR4 positive circulating tumor cells in prostate cancer patients during radiotherapy. International Journal of Cancer [Epub ahead of print]. doi: 10.1002/ijc.34457 https://onlinelibrary.wiley.com/doi/10.1002/ijc.34457 - Open Access 2 februar 2023
  • Köstler, C., Polzer, B., Alberter, B. (2024). Circulating Tumor Cell Enrichment and Single-Cell Isolation Combining the CellSearch((R)) and DEPArray Systems. Methods in Molecular Biology 2752: 11-42. doi: 10.1007/978-1-0716-3621-3_2 https://link.springer.com/protocol/10.1007/978-1-0716-3621-3_2
  • Nowak, J., Bentele, M., Kutle, I., Zimmermann, K., Luhmann, J. L., Steinemann, D., Kloess, S., Koehl, U., Rossberg, W., Ahmed, A., Schaudien, D., Neubert, L., Kamp, J. C., Kuehnel, M. P., Warnecke, A., Schambach, A., Morgan, M. (2023). CAR-NK Cells Targeting HER1 (EGFR) Show Efficient Anti-Tumor Activity against Head and Neck Squamous Cell Carcinoma (HNSCC). Cancers 15(12): 3169. doi: 10.3390/cancers15123169 https://www.mdpi.com/2072-6694/15/12/3169  - Open Access
  • Reduzzi, C., Vismara, M., Schamberger, T., Silvestri, M., Motta, R., Polzer, B. M., Cappelletti, V. (2024). Isolation and Genomic Analysis of Circulating Tumor Cell Clusters in Cancer Patients. Methods in Molecular Biology 2752: 101-117. doi: 10.1007/978-1-0716-3621-3_7 https://link.springer.com/protocol/10.1007/978-1-0716-3621-3_7
  • Treitschke, S., Weidele, K., Varadarajan, A. R., Feliciello, G., Warfsmann, J., Vorbeck, S., Polzer, B., Botteron, C., Hoffmann, M., Dechand, V., Mederer, T., Weber, F., Werner-Klein, M., Robold, T., Hofmann, H. S., Werno, C., Klein, C. A. (2023). Ex vivo expansion of lung cancer-derived disseminated cancer cells from lymph nodes identifies cells associated with metastatic progression. International Journal of Cancer [Epub ahead of print]. doi: 10.1002/ijc.34658 https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.34658 - Open Access