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  1. Article ; Online: Immunomodulatory potential of mesenchymal stromal cell-derived extracellular vesicles in chondrocyte inflammation.

    Ossendorff, Robert / Grad, Sibylle / Tertel, Tobias / Wirtz, Dieter C / Giebel, Bernd / Börger, Verena / Schildberg, Frank A

    Frontiers in immunology

    2023  Volume 14, Page(s) 1198198

    Abstract: Introduction: Osteoarthritis (OA) affects a large percentage of the population worldwide. Current surgical and nonsurgical concepts for treating OA only result in symptom-modifying effects. However, there is no disease-modifying therapy available. ... ...

    Abstract Introduction: Osteoarthritis (OA) affects a large percentage of the population worldwide. Current surgical and nonsurgical concepts for treating OA only result in symptom-modifying effects. However, there is no disease-modifying therapy available. Extracellular vesicles released by mesenchymal stem/stromal cells (MSC-EV) are promising agents to positively influence joint homeostasis in the osteoarthritic surroundings. This pilot study aimed to investigate the effect of characterized MSC-EVs on chondrogenesis in a 3D chondrocyte inflammation model with the pro-inflammatory cytokine TNFα.
    Methods: Bovine articular chondrocytes were expanded and transferred into pellet culture at passage 3. TNFα, human MSC-EV preparations (MSC-EV batches 41.5-EV
    Results: TNFα supplementation resulted in catabolic stimulation with increased levels of NO and IL-6, upregulation of catabolic gene expression, and downregulation of anabolic markers. These findings were supported by a decrease in matrix differentiation (COL-II). Supplementation of EVs resulted in an upregulation of the chondrogenic marker PRG-4. All MSC-EV preparations significantly increased GAG retention per pellet. In contrast, catabolic markers and IL-8 expression were upregulated by 41.5-EV
    Discussion: MSC-EVs can positively influence chondrocyte matrix production in pro-inflammatory surroundings, but can also stimulate inflammation. In this study MSC-EV 41.5-EV
    MeSH term(s) Animals ; Cattle ; Humans ; Chondrocytes/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Pilot Projects ; Cells, Cultured ; Inflammation/metabolism ; Osteoarthritis/metabolism ; Glycosaminoglycans/metabolism ; Mesenchymal Stem Cells/metabolism ; Extracellular Vesicles/metabolism
    Chemical Substances Tumor Necrosis Factor-alpha ; Interleukin-6 ; Interleukin-8 ; Glycosaminoglycans
    Language English
    Publishing date 2023-07-26
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1198198
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Qualification of a multidonor mixed lymphocyte reaction assay for the functional characterization of immunomodulatory extracellular vesicles.

    Bremer, Michel / Nardi Bauer, Fabiola / Tertel, Tobias / Dittrich, Robin / Horn, Peter A / Börger, Verena / Giebel, Bernd

    Cytotherapy

    2023  Volume 25, Issue 8, Page(s) 847–857

    Abstract: Background aims: Extracellular vesicles (EVs), including exosomes and microvesicles, are released by almost all cells and found in all body fluids. Unknown proportions of EVs transmit specific information from their cells of origin to specific target ... ...

    Abstract Background aims: Extracellular vesicles (EVs), including exosomes and microvesicles, are released by almost all cells and found in all body fluids. Unknown proportions of EVs transmit specific information from their cells of origin to specific target cells and are key mediators in intercellular communication processes. Depending on their origin, EVs can modulate immune responses, either acting as pro- or anti-inflammatory. With the aim to analyze the immunomodulating activities of EV preparations, especially those from mesenchymal stromal cells (MSCs) in vitro, a multi-donor mixed lymphocyte reaction (mdMLR) assay was established and stressed for its reproducibility.
    Methods: To this end, human peripheral blood-derived mononuclear cells (PBMCs) of 12 different healthy donors were pooled warranting mutual allogeneic cross-reactivity, even following an optimized freezing and thawing procedure. After thawing, mixed PBMCs were cultured for 5 days in the absence or presence of EVs to be tested. Reflecting allogeneic reactions, in the absence of EVs, pooled PBMCs form characteristic satellite colonies whose appearance can be modulated by EVs. More quantifiable, the strength of the allogenic reaction is reflected by the content of activated CD4 and CD8 T cells being recognized by means of their CD25 and CD54 expression.
    Results: Of note, connected to the use of primary cells, independent multi-donor PBMC pools differed in their capability to activate their cultured T cells. Thus, throughout the study, only pooled PBMC batches were used whose activated T-cell contents exceeded 25% of the total T-cell population at culture day 5 and whose contents were reproducibly reduced in the presence of immunomodulatory active MSC-EVs. T-cell activation-suppressing effects of the MSC-EV preparations tested were in all cases accompanied by the impact on monocytes. In the presence of immunomodulatory active MSC-EVs, more monocytes were harvested from mdMLR cultures than in their absence. Furthermore, in the absence of immunomodulatory EVs, most monocytes appeared as non-classical (CD14
    Conclusions: Overall, the obtained results qualify the mdMLR assay as a robust experimental tool for the evaluation of immunomodulatory potentials of given MSC-EV samples. However, further assay development is required to develop and qualify an authority-acceptable potency assay for clinically applicable MSC-EV products.
    MeSH term(s) Humans ; Leukocytes, Mononuclear ; Lymphocyte Culture Test, Mixed ; Reproducibility of Results ; Extracellular Vesicles/metabolism ; Immunity
    Language English
    Publishing date 2023-04-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2039821-9
    ISSN 1477-2566 ; 1465-3249
    ISSN (online) 1477-2566
    ISSN 1465-3249
    DOI 10.1016/j.jcyt.2023.03.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5601: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Conference proceedings: Immunomodulatory potential of mesenchymal stromal cell-derived extracellular vesicles in chondrocyte inflammation

    Ossendorff, Robert / Grad, Sibylle / Tertel, Tobias / Wirtz, Dieter C. / Giebel, Bernd / Börger, Verena / Schildberg, Frank A.

    2023  , Page(s) BS44–2862

    Event/congress Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2023); Berlin; ; Berufsverband für Orthopädie und Unfallchirurgie; 2023
    Keywords Medizin, Gesundheit ; mesenchymal stromal cells ; MSC ; extracellular vesicles ; EV ; chondrocytes ; inflammation ; osteoarthritis
    Publishing date 2023-10-23
    Publisher German Medical Science GMS Publishing House; Düsseldorf
    Document type Conference proceedings
    DOI 10.3205/23dkou669
    Database German Medical Science

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  4. Book ; Thesis: Charakterisierung von Tumorstammzellen und Tumorstroma des Nierenzellkarzinoms

    Börger, Verena

    2011  

    Author's details vorgelegt von Verena Börger
    Language German
    Size 186 S., Ill., graph. Darst., 21 cm
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Univ., Diss.--Düsseldorf, 2012
    Database Special collection on veterinary medicine and general parasitology

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  5. Article ; Online: Scaled Isolation of Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles.

    Börger, Verena / Staubach, Simon / Dittrich, Robin / Stambouli, Oumaima / Giebel, Bernd

    Current protocols in stem cell biology

    2020  Volume 55, Issue 1, Page(s) e128

    Abstract: Mesenchymal stem/stromal cells (MSCs) provide therapeutic effects in many diseases. Contrary to initial hypotheses, they act in a paracrine rather than a cellular manner. To this end, extracellular vesicles (EVs) have been found to mediate the ... ...

    Abstract Mesenchymal stem/stromal cells (MSCs) provide therapeutic effects in many diseases. Contrary to initial hypotheses, they act in a paracrine rather than a cellular manner. To this end, extracellular vesicles (EVs) have been found to mediate the therapeutic effects, even when harvested from MSC-conditioned cell culture supernatants. Lacking self-replicating activity and being so small that MSC-EV preparations can be sterilized by filtration, EVs provide several advantages as therapeutic agents over cellular therapeutics. At present, methods allowing EV preparation from larger volumes are scarce and regularly require special equipment. We have developed a polyethylene glycol-based precipitation protocol allowing extraction of EVs from several liters of conditioned medium. MSC-EVs prepared with this method have been successfully applied to a human graft-versus-host disease patient and to several animal models. Although the method comes with its own limitations, it is extremely helpful for the initial evaluation of EV-based therapeutic approaches. Here, we introduce the technique in detail and discuss all critical steps. © 2020 The Authors. Basic Protocol 1: Preparation of MSC-conditioned medium for scaled MSC-EV production Basic Protocol 2: PEG precipitation OF MSC-EV from MSC-conditioned medium.
    MeSH term(s) Animals ; Cells, Cultured ; Culture Media, Conditioned ; Extracellular Vesicles/metabolism ; Humans ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism
    Chemical Substances Culture Media, Conditioned
    Language English
    Publishing date 2020-10-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1938-8969
    ISSN (online) 1938-8969
    DOI 10.1002/cpsc.128
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Conference proceedings: Therapeutischer Einfluss extrazellulärer Vesikel (EV) aus mesenchymalen Stamm-/Stromazellen (MSC) auf die partikelinduzierte Osteolyse im murinen Calvariamodell

    Polan, Christina / Börger, Verena / Hilken, Gero / Moraitis, Alexandros / Lückerath, Katharina / Staniszewska, Magdalena / Behnke, Verena / Burggraf, Manuel / Meyer, Heinz-Lothar / Kauther, Max Daniel / Dudda, Marcel / Herten, Monika

    2023  , Page(s) AB54–2104

    Event/congress Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2023); Berlin; ; Berufsverband für Orthopädie und Unfallchirurgie; 2023
    Keywords Medizin, Gesundheit ; aseptische Osteolyse ; Partikelkrankheit ; extrazellulärer Vesikel ; Calvariamodell
    Publishing date 2023-10-23
    Publisher German Medical Science GMS Publishing House; Düsseldorf
    Document type Conference proceedings
    DOI 10.3205/23dkou261
    Database German Medical Science

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  7. Article ; Online: The Employment of the Surface Plasmon Resonance (SPR) Microscopy Sensor for the Detection of Individual Extracellular Vesicles and Non-Biological Nanoparticles.

    Sharar, Nour / Wüstefeld, Konstantin / Talukder, Rahat Morad / Skolnik, Julija / Kaufmann, Katharina / Giebel, Bernd / Börger, Verena / Nolte, Friedrich / Watzl, Carsten / Weichert, Frank / Hergenröder, Roland / Shpacovitch, Victoria

    Biosensors

    2023  Volume 13, Issue 4

    Abstract: A wide-field surface plasmon resonance (SPR) microscopy sensor employs the surface plasmon resonance phenomenon to detect individual biological and non-biological nanoparticles. This sensor enables the detection, sizing, and quantification of biological ... ...

    Abstract A wide-field surface plasmon resonance (SPR) microscopy sensor employs the surface plasmon resonance phenomenon to detect individual biological and non-biological nanoparticles. This sensor enables the detection, sizing, and quantification of biological nanoparticles (bioNPs), such as extracellular vesicles (EVs), viruses, and virus-like particles. The selectivity of bioNP detection does not require biological particle labeling, and it is achieved via the functionalization of the gold sensor surface by target-bioNP-specific antibodies. In the current work, we demonstrate the ability of SPR microscopy sensors to detect, simultaneously, silica NPs that differ by four times in size. Employed silica particles are close in their refractive index to bioNPs. The literature reports the ability of SPR microscopy sensors to detect the binding of lymphocytes (around 10 μm objects) to the sensor surface. Taken together, our findings and the results reported in the literature indicate the power of SPR microscopy sensors to detect bioNPs that differ by at least two orders in size. Modifications of the optical sensor scheme, such as mounting a concave lens, help to achieve homogeneous illumination of a gold sensor chip surface. In the current work, we also characterize the improved magnification factor of the modified SPR instrument. We evaluate the effectiveness of the modified and the primary version of the SPR microscopy sensors in detecting EVs isolated via different approaches. In addition, we demonstrate the possibility of employing translation and rotation stepper motors for precise adjustments of the positions of sensor optical elements-prism and objective-in the primary version of the SPR microscopy sensor instrument, and we present an algorithm to establish effective sensor-actuator coupling.
    MeSH term(s) Surface Plasmon Resonance/methods ; Microscopy ; Nanoparticles/chemistry ; Extracellular Vesicles ; Silicon Dioxide ; Gold ; Employment
    Chemical Substances Silicon Dioxide (7631-86-9) ; Gold (7440-57-5)
    Language English
    Publishing date 2023-04-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662125-3
    ISSN 2079-6374 ; 2079-6374
    ISSN (online) 2079-6374
    ISSN 2079-6374
    DOI 10.3390/bios13040472
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles.

    Giebel, Bernd / Kordelas, Lambros / Börger, Verena

    Stem cell investigation

    2017  Volume 4, Page(s) 84

    Abstract: Within the last two decades mesenchymal stem/stromal cells (MSCs) emerged after hematopoietic stem cells as the second most investigated and applied somatic stem cell entity so far. MSCs mediate immunosuppressive as well as pro-regenerative activities. ... ...

    Abstract Within the last two decades mesenchymal stem/stromal cells (MSCs) emerged after hematopoietic stem cells as the second most investigated and applied somatic stem cell entity so far. MSCs mediate immunosuppressive as well as pro-regenerative activities. Against the initial assumption, MSCs may not primarily exert their therapeutic functions in a cellular but rather in a paracrine manner. Here, extracellular vesicles (EVs), such as exosomes and microvesicles, have been identified as major mediators of these paracrine effects. Meanwhile, MSC-EVs have been applied to an increasing amount of different animal models and were tested in a patient suffering from steroid-refractory acute graft-versus-host disease (acute GvHD) as well as in a patient cohort with chronic kidney disease. So far, the MSC-EV administration appears to be safe in humans and all tested animal models. Improvements were reported in all settings. Thus, MSC-EVs appear as promising novel therapeutic agents which might help to improve disease associated symptoms in millions of patients. Here, we review some of the milestones in the field, briefly discuss challenges and highlight clinical aspects of acute GvHD and its treatment with MSCs and MSC-EVs.
    Language English
    Publishing date 2017-10-24
    Publishing country China
    Document type Journal Article ; Review
    ZDB-ID 2884645-X
    ISSN 2313-0792 ; 2306-9759
    ISSN (online) 2313-0792
    ISSN 2306-9759
    DOI 10.21037/sci.2017.09.06
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Mesenchymal stromal cell-derived small extracellular vesicles promote neurological recovery and brain remodeling after distal middle cerebral artery occlusion in aged rats.

    Dumbrava, Danut-Adrian / Surugiu, Roxana / Börger, Verena / Ruscu, Mihai / Tertel, Tobias / Giebel, Bernd / Hermann, Dirk M / Popa-Wagner, Aurel

    GeroScience

    2021  Volume 44, Issue 1, Page(s) 293–310

    Abstract: Small extracellular vesicles (sEVs) obtained from mesenchymal stromal cells (MSCs) promote neurological recovery after middle cerebral artery occlusion (MCAO) in young rodents. Ischemic stroke mainly affects aged humans. MSC-sEV effects on stroke ... ...

    Abstract Small extracellular vesicles (sEVs) obtained from mesenchymal stromal cells (MSCs) promote neurological recovery after middle cerebral artery occlusion (MCAO) in young rodents. Ischemic stroke mainly affects aged humans. MSC-sEV effects on stroke recovery in aged rodents had not been assessed. In a head-to-head comparison, we exposed young (4-5 months) and aged (19-20 months) male Sprague-Dawley rats to permanent distal MCAO. At 24 h, 3 and 7 days post-stroke, vehicle or MSC-sEVs (2 × 10
    MeSH term(s) Animals ; Brain/blood supply ; Disease Models, Animal ; Extracellular Vesicles ; Infarction, Middle Cerebral Artery ; Male ; Mesenchymal Stem Cells ; Rats ; Rats, Sprague-Dawley
    Language English
    Publishing date 2021-11-10
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2886586-8
    ISSN 2509-2723 ; 2509-2715
    ISSN (online) 2509-2723
    ISSN 2509-2715
    DOI 10.1007/s11357-021-00483-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1502: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  10. Article: Mesenchymal Stromal Cell-Derived Extracellular Vesicles Reduce Neuroinflammation, Promote Neural Cell Proliferation and Improve Oligodendrocyte Maturation in Neonatal Hypoxic-Ischemic Brain Injury.

    Kaminski, Nicole / Köster, Christian / Mouloud, Yanis / Börger, Verena / Felderhoff-Müser, Ursula / Bendix, Ivo / Giebel, Bernd / Herz, Josephine

    Frontiers in cellular neuroscience

    2020  Volume 14, Page(s) 601176

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2020-12-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2020.601176
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