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  1. Article ; Online: Mesenchymal Stem Cell Conditioned Medium Modulates Inflammation in Tenocytes: Complete Conditioned Medium Has Superior Therapeutic Efficacy than Its Extracellular Vesicle Fraction.

    Soukup, Robert / Gerner, Iris / Mohr, Thomas / Gueltekin, Sinan / Grillari, Johannes / Jenner, Florien

    International journal of molecular sciences

    2023  Volume 24, Issue 13

    Abstract: Tendinopathy, a prevalent overuse injury, lacks effective treatment options, leading to a significant impact on quality of life and socioeconomic burden. Mesenchymal stem/stromal cells (MSCs) and their secretome, including conditioned medium (CM) and ... ...

    Abstract Tendinopathy, a prevalent overuse injury, lacks effective treatment options, leading to a significant impact on quality of life and socioeconomic burden. Mesenchymal stem/stromal cells (MSCs) and their secretome, including conditioned medium (CM) and extracellular vesicles (EVs), have shown promise in tissue regeneration and immunomodulation. However, it remains unclear which components of the secretome contribute to their therapeutic effects. This study aimed to compare the efficacy of CM, EVs, and the soluble protein fraction (PF) in treating inflamed tenocytes. CM exhibited the highest protein and particle concentrations, followed by PF and EVs. Inflammation significantly altered gene expression in tenocytes, with CM showing the most distinct separation from the inflamed control group. Treatment with CM resulted in the most significant differential gene expression, with both upregulated and downregulated genes related to inflammation and tissue regeneration. EV treatment also demonstrated a therapeutic effect, albeit to a lesser extent. These findings suggest that CM holds superior therapeutic efficacy compared with its EV fraction alone, emphasizing the importance of the complete secretome in tendon injury treatment.
    MeSH term(s) Humans ; Culture Media, Conditioned/pharmacology ; Culture Media, Conditioned/metabolism ; Tenocytes/metabolism ; Quality of Life ; Extracellular Vesicles/metabolism ; Inflammation/metabolism ; Proteins/metabolism ; Mesenchymal Stem Cells/metabolism
    Chemical Substances Culture Media, Conditioned ; Proteins
    Language English
    Publishing date 2023-06-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241310857
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Characterisation of Extracellular Vesicles from Equine Mesenchymal Stem Cells.

    Soukup, Robert / Gerner, Iris / Gültekin, Sinan / Baik, Hayeon / Oesterreicher, Johannes / Grillari, Johannes / Jenner, Florien

    International journal of molecular sciences

    2022  Volume 23, Issue 10

    Abstract: Extracellular vesicles (EVs) are nanosized lipid bilayer-encapsulated particles secreted by virtually all cell types. EVs play an essential role in cellular crosstalk in health and disease. The cellular origin of EVs determines their composition and ... ...

    Abstract Extracellular vesicles (EVs) are nanosized lipid bilayer-encapsulated particles secreted by virtually all cell types. EVs play an essential role in cellular crosstalk in health and disease. The cellular origin of EVs determines their composition and potential therapeutic effect. Mesenchymal stem/stromal cell (MSC)-derived EVs have shown a comparable therapeutic potential to their donor cells, making them a promising tool for regenerative medicine. The therapeutic application of EVs circumvents some safety concerns associated with the transplantation of viable, replicating cells and facilitates the quality-controlled production as a ready-to-go, off-the-shelf biological therapy. Recently, the International Society for Extracellular Vesicles (ISEV) suggested a set of minimal biochemical, biophysical and functional standards to define extracellular vesicles and their functions to improve standardisation in EV research. However, nonstandardised EV isolation methods and the limited availability of cross-reacting markers for most animal species restrict the application of these standards in the veterinary field and, therefore, the species comparability and standardisation of animal experiments. In this study, EVs were isolated from equine bone-marrow-derived MSCs using two different isolation methods, stepwise ultracentrifugation and size exclusion chromatography, and minimal experimental requirements for equine EVs were established and validated. Equine EVs were characterised using a nanotracking analysis, fluorescence-triggered flow cytometry, Western blot and transelectron microscopy. Based on the ISEV standards, minimal criteria for defining equine EVs are suggested as a baseline to allow the comparison of EV preparations obtained by different laboratories.
    MeSH term(s) Animals ; Cells, Cultured ; Chromatography, Gel ; Extracellular Vesicles/metabolism ; Horses ; Mesenchymal Stem Cells/metabolism ; Ultracentrifugation
    Language English
    Publishing date 2022-05-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23105858
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: STAT3 promotes melanoma metastasis by CEBP-induced repression of the MITF pathway.

    Swoboda, Alexander / Soukup, Robert / Eckel, Oliver / Kinslechner, Katharina / Wingelhofer, Bettina / Schörghofer, David / Sternberg, Christina / Pham, Ha T T / Vallianou, Maria / Horvath, Jaqueline / Stoiber, Dagmar / Kenner, Lukas / Larue, Lionel / Poli, Valeria / Beermann, Friedrich / Yokota, Takashi / Kubicek, Stefan / Krausgruber, Thomas / Rendeiro, André F /
    Bock, Christoph / Zenz, Rainer / Kovacic, Boris / Aberger, Fritz / Hengstschläger, Markus / Petzelbauer, Peter / Mikula, Mario / Moriggl, Richard

    Oncogene

    2020  Volume 40, Issue 6, Page(s) 1091–1105

    Abstract: Metastatic melanoma is hallmarked by its ability of phenotype switching to more slowly proliferating, but highly invasive cells. Here, we tested the impact of signal transducer and activator of transcription 3 (STAT3) on melanoma progression in ... ...

    Abstract Metastatic melanoma is hallmarked by its ability of phenotype switching to more slowly proliferating, but highly invasive cells. Here, we tested the impact of signal transducer and activator of transcription 3 (STAT3) on melanoma progression in association with melanocyte inducing transcription factor (MITF) expression levels. We established a mouse melanoma model for deleting Stat3 in melanocytes with specific expression of human hyperactive NRAS
    MeSH term(s) Animals ; CCAAT-Enhancer-Binding Protein-beta/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Disease Models, Animal ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Melanocytes/drug effects ; Melanoma/genetics ; Melanoma/pathology ; Mice ; Microphthalmia-Associated Transcription Factor/genetics ; Neoplasm Metastasis ; STAT3 Transcription Factor/genetics ; Signal Transduction/drug effects
    Chemical Substances CCAAT-Enhancer-Binding Protein-beta ; Cebpb protein, mouse ; Microphthalmia-Associated Transcription Factor ; Mitf protein, mouse ; STAT3 Transcription Factor ; Stat3 protein, mouse
    Language English
    Publishing date 2020-12-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/s41388-020-01584-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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