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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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<affiliation>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</affiliation> </creator> <creator> <creatorName>Quarta, Alessandra</creatorName> <givenName>Alessandra</givenName> <familyName>Quarta</familyName> <affiliation>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</affiliation> </creator> <creator> <creatorName>Daans, Jasmijn</creatorName> <givenName>Jasmijn</givenName> <familyName>Daans</familyName> <affiliation>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</affiliation> </creator> <creator> <creatorName>Dooley, Dearbhaile</creatorName> <givenName>Dearbhaile</givenName> <familyName>Dooley</familyName> <affiliation>Department of Morphology, Biomedical Research Institute, Hasselt University, Agoralaan building C, 3590, Diepenbeek, Belgium</affiliation> </creator> <creator> <creatorName>Lemmens, Evi</creatorName> <givenName>Evi</givenName> <familyName>Lemmens</familyName> <affiliation>Department of Morphology, Biomedical Research Institute, Hasselt University, Agoralaan building C, 3590, Diepenbeek, Belgium</affiliation> </creator> <creator> <creatorName>Praet, Jelle</creatorName> <givenName>Jelle</givenName> <familyName>Praet</familyName> <affiliation>Bio-Imaging Laboratory, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</affiliation> </creator> <creator> <creatorName>De Vocht, Nathalie</creatorName> <givenName>Nathalie</givenName> <familyName>De Vocht</familyName> <affiliation>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</affiliation> </creator> <creator> <creatorName>Reekmans, Kristien</creatorName> <givenName>Kristien</givenName> <familyName>Reekmans</familyName> <affiliation>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</affiliation> </creator> <creator> <creatorName>Santermans, Eva</creatorName> <givenName>Eva</givenName> <familyName>Santermans</familyName> <affiliation>Center for Statistics, I-Biostat, Hasselt University, Agoralaan building D, 3590, Diepenbeek, Belgium</affiliation> </creator> <creator> <creatorName>Hens, Niel</creatorName> <givenName>Niel</givenName> <familyName>Hens</familyName> <affiliation>Center for Statistics, I-Biostat, Hasselt University, Agoralaan building D, 3590, Diepenbeek, Belgium</affiliation> </creator> <creator> <creatorName>Goossens, Herman</creatorName> <givenName>Herman</givenName> <familyName>Goossens</familyName> <affiliation>Vaccine and Infectious Disease Institute, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</affiliation> </creator> <creator> <creatorName>Verhoye, Marleen</creatorName> <givenName>Marleen</givenName> <familyName>Verhoye</familyName> <affiliation>Bio-Imaging Laboratory, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</affiliation> </creator> <creator> <creatorName>Van der Linden, Annemie</creatorName> <givenName>Annemie</givenName> <familyName>Van der Linden</familyName> <affiliation>Bio-Imaging Laboratory, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</affiliation> </creator> <creator> <creatorName>Berneman, Zwi</creatorName> <givenName>Zwi</givenName> <familyName>Berneman</familyName> <affiliation>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</affiliation> </creator> <creator> <creatorName>Hendrix, Sven</creatorName> <givenName>Sven</givenName> <familyName>Hendrix</familyName> <affiliation>Department of Morphology, Biomedical Research Institute, Hasselt University, Agoralaan building C, 3590, Diepenbeek, Belgium</affiliation> </creator> <creator> <creatorName>Ponsaerts, Peter</creatorName> <givenName>Peter</givenName> <familyName>Ponsaerts</familyName> <affiliation>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</affiliation> </creator> </creators> <titles> <title>Intracerebral transplantation of interleukin 13-producing mesenchymal stem cells limits microgliosis, oligodendrocyte loss and demyelination in the cuprizone mouse model</title> </titles> <publisher>Zenodo</publisher> <publicationYear>2016</publicationYear> <subjects> <subject>Interleukin 13</subject> <subject>Mesenchymal stem cells</subject> <subject>Neuroinflammation</subject> <subject>Transplantation</subject> <subject>Magnetic resonance imaging</subject> </subjects> <dates> <date dateType="Issued">2016-11-09</date> </dates> <resourceType resourceTypeGeneral="Text">Journal article</resourceType> <alternateIdentifiers> <alternateIdentifier alternateIdentifierType="url">https://zenodo.org/record/166404</alternateIdentifier> </alternateIdentifiers> <relatedIdentifiers> <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1186/s12974-016-0756-7</relatedIdentifier> <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/ecfunded</relatedIdentifier> <relatedIdentifier relatedIdentifierType="URL" relationType="IsPartOf">https://zenodo.org/communities/fp7-bmc</relatedIdentifier> </relatedIdentifiers> <rightsList> <rights rightsURI="https://creativecommons.org/licenses/by/4.0/legalcode">Creative Commons Attribution 4.0 International</rights> <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights> </rightsList> <descriptions> <description descriptionType="Abstract"><p><strong>Background: </strong>Promoting the neuroprotective and repair-inducing effector functions of microglia and macrophages, by means of M2 polarisation or alternative activation, is expected to become a new therapeutic approach for central nervous system (CNS) disorders in which detrimental pro-inflammatory microglia and/or macrophages display a major contribution to the neuropathology. 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></description> </descriptions> <fundingReferences> <fundingReference> <funderName>European Commission</funderName> <funderIdentifier funderIdentifierType="Crossref Funder ID">10.13039/501100000780</funderIdentifier> <awardNumber awardURI="info:eu-repo/grantAgreement/EC/FP7/278850/">278850</awardNumber> <awardTitle>Imaging of Neuroinflammation in Neurodegenerative Diseases</awardTitle> </fundingReference> </fundingReferences> </resource>
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