November 9, 2016 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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  <identifier identifierType="URL">https://zenodo.org/record/166404</identifier>
  <creators>
    <creator>
      <creatorName>Le Blon, Debbie</creatorName>
      <givenName>Debbie</givenName>
      <familyName>Le Blon</familyName>
      <affiliation>Laboratory of Experimental Hematology, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</affiliation>
    </creator>
    <creator>
      <creatorName>Guglielmetti, Caroline</creatorName>
      <givenName>Caroline</givenName>
      <familyName>Guglielmetti</familyName>
      <affiliation>Bio-Imaging Laboratory, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium</affiliation>
    </creator>
    <creator>
      <creatorName>Hoornaert, Chloé</creatorName>
      <givenName>Chloé</givenName>
      <familyName>Hoornaert</familyName>
      <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>
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  <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="http://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">&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;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).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In the first experimental setup, control MSC and IL13-MSC were grafted in the CNS of eGFP&lt;sup&gt;+&lt;/sup&gt; 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 &lt;i&gt;splenium&lt;/i&gt; of the &lt;i&gt;corpus callosum&lt;/i&gt; in wild-type C57BL/6 mice and in C57BL/6 CX&lt;sub&gt;3&lt;/sub&gt;CR1&lt;sup&gt;eGFP/+&lt;/sup&gt;CCR2&lt;sup&gt;RFP/+&lt;/sup&gt; 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 &lt;i&gt;T&lt;/i&gt; &lt;sub&gt;2&lt;/sub&gt;-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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;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.&lt;/p&gt;</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>
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