Journal article Open Access
Le Blon, Debbie; Guglielmetti, Caroline; Hoornaert, Chloé; Quarta, Alessandra; Daans, Jasmijn; Dooley, Dearbhaile; Lemmens, Evi; Praet, Jelle; De Vocht, Nathalie; Reekmans, Kristien; Santermans, Eva; Hens, Niel; Goossens, Herman; Verhoye, Marleen; Van der Linden, Annemie; Berneman, Zwi; Hendrix, Sven; Ponsaerts, Peter
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In this study, we present a novel in vivo approach using intracerebral grafting of mesenchymal stem cells (MSC) genetically engineered to secrete interleukin 13 (IL13-MSC).</p><p><strong>Methods: </strong>In the first experimental setup, control MSC and IL13-MSC were grafted in the CNS of eGFP<sup>+</sup> bone marrow chimaeric C57BL/6 mice to histologically evaluate IL13-mediated expression of several markers associated with alternative activation, including arginase1 and Ym1, on MSC graft-recognising microglia and MSC graft-infiltrating macrophages. In the second experimental setup, IL13-MSC were grafted on the right side (or on both the right and left sides) of the <i>splenium</i> of the <i>corpus callosum</i> in wild-type C57BL/6 mice and in C57BL/6 CX<sub>3</sub>CR1<sup>eGFP/+</sup>CCR2<sup>RFP/+</sup> transgenic mice. Next, CNS inflammation and demyelination was induced by means of a cuprizone-supplemented diet. The influence of IL13-MSC grafting on neuropathological alterations was monitored by non-invasive <i>T</i> <sub>2</sub>-weighted magnetic resonance imaging (MRI) and quantitative histological analyses, as compared to cuprizone-treated mice with control MSC grafts and/or cuprizone-treated mice without MSC injection.</p><p><strong>Results: </strong>In the first part of this study, we demonstrate that MSC graft-associated microglia and MSC graft-infiltrating macrophages are forced into alternative activation upon grafting of IL13-MSC, but not upon grafting of control MSC. In the second part of this study, we demonstrate that grafting of IL13-MSC, in addition to the recruitment of M2 polarised macrophages, limits cuprizone-induced microgliosis, oligodendrocyte death and demyelination. Furthermore, we here demonstrate that injection of IL13-MSC at both sides of the splenium leads to a superior protective effect as compared to a single injection at one side of the splenium.</p><p><strong>Conclusions: </strong>Controlled and localised production of IL13 by means of intracerebral MSC grafting has the potential to modulate cell graft- and pathology-associated microglial/macrophage responses, and to interfere with oligodendrocyte death and demyelinating events in the cuprizone mouse model.</p>", "license": { "id": "CC-BY-4.0" }, "title": "Intracerebral transplantation of interleukin 13-producing mesenchymal stem cells limits microgliosis, oligodendrocyte loss and demyelination in the cuprizone mouse model", "journal": { "volume": "13", "issue": "1", "pages": "288", "title": "Journal of Neuroinflammation" }, "relations": { "version": [ { "count": 1, "index": 0, "parent": { "pid_type": "recid", "pid_value": "661963" }, "is_last": true, "last_child": { "pid_type": "recid", "pid_value": "166404" } } ] }, "communities": [ { "id": "ecfunded" }, { "id": "fp7-bmc" } ], "grants": [ { "code": "278850", "links": { "self": "https://zenodo.org/api/grants/10.13039/501100000780::278850" }, "title": "Imaging of Neuroinflammation in Neurodegenerative Diseases", "acronym": "INMIND", "program": "FP7", "funder": { "doi": "10.13039/501100000780", "acronyms": [], "name": "European Commission", "links": { "self": "https://zenodo.org/api/funders/10.13039/501100000780" } } } ], "keywords": [ "Interleukin 13", "Mesenchymal stem cells", "Neuroinflammation", "Transplantation", "Magnetic resonance imaging" ], "publication_date": "2016-11-09", "creators": [ { "affiliation": "Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium", "name": "Le Blon, Debbie" }, { "affiliation": "Bio-Imaging Laboratory, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium", "name": "Guglielmetti, Caroline" }, { "affiliation": "Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium", "name": "Hoornaert, Chlo\u00e9" }, { "affiliation": "Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium", "name": "Quarta, Alessandra" }, { "affiliation": "Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium", "name": "Daans, Jasmijn" }, { "affiliation": "Department of Morphology, Biomedical Research Institute, Hasselt University, Agoralaan building C, 3590, Diepenbeek, Belgium", "name": "Dooley, Dearbhaile" }, { "affiliation": "Department of Morphology, Biomedical Research Institute, Hasselt University, Agoralaan building C, 3590, Diepenbeek, Belgium", "name": "Lemmens, Evi" }, { "affiliation": "Bio-Imaging Laboratory, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium", "name": "Praet, Jelle" }, { "affiliation": "Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium", "name": "De Vocht, Nathalie" }, { "affiliation": "Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium", "name": "Reekmans, Kristien" }, { "affiliation": "Center for Statistics, I-Biostat, Hasselt University, Agoralaan building D, 3590, Diepenbeek, Belgium", "name": "Santermans, Eva" }, { "affiliation": "Center for Statistics, I-Biostat, Hasselt University, Agoralaan building D, 3590, Diepenbeek, Belgium", "name": "Hens, Niel" }, { "affiliation": "Vaccine and Infectious Disease Institute, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium", "name": "Goossens, Herman" }, { "affiliation": "Bio-Imaging Laboratory, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium", "name": "Verhoye, Marleen" }, { "affiliation": "Bio-Imaging Laboratory, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium", "name": "Van der Linden, Annemie" }, { "affiliation": "Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium", "name": "Berneman, Zwi" }, { "affiliation": "Department of Morphology, Biomedical Research Institute, Hasselt University, Agoralaan building C, 3590, Diepenbeek, Belgium", "name": "Hendrix, Sven" }, { "affiliation": "Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium", "name": "Ponsaerts, Peter" } ], "access_right": "open", "resource_type": { "subtype": "article", "type": "publication", "title": "Journal article" } } }
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