Intranasal delivery of central nervous system-retargeted human mesenchymal stromal cells prolongs treatment efficacy of experimental autoimmune encephalomyelitis

Authors

  • Moa Fransson,

    Corresponding author
    1. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
    • Correspondence: Moa Fransson, Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory C11 entrance floor, Dag Hammarskjoldsv 20, 751 85 Uppsala, Sweden. Email: moa.fransson@igp.uu.se

      Senior author: Angelica Loskog,email: angelica.loskog@igp.uu.se

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    • These authors contributed equally to this work.
  • Elena Piras,

    1. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
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    • These authors contributed equally to this work.
  • Hao Wang,

    1. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
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  • Joachim Burman,

    1. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
    2. Department of Neuroscience, Uppsala University and University Hospital, Uppsala, Sweden
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  • Ida Duprez,

    1. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
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  • Robert A. Harris,

    1. Department of Clinical Neurosciences, Karolinska Institutet, Applied Immunology, Centre for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
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  • Katarina LeBlanc,

    1. Division of Clinical Immunology, Karolinska Institutet, Stockholm, Sweden
    2. Haematology Centre, Karolinska University Hospital, Huddinge, Sweden
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  • Peetra U. Magnusson,

    1. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
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  • Eva Brittebo,

    1. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
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  • Angelica S. I. Loskog

    1. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
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Summary

Treatment with mesenchymal stromal cells (MSCs) is currently of interest for a number of diseases including multiple sclerosis. MSCs are known to target inflamed tissues, but in a therapeutic setting their systemic administration will lead to few cells reaching the brain. We hypothesized that MSCs may target the brain upon intranasal administration and persist in central nervous system (CNS) tissue if expressing a CNS-targeting receptor. To demonstrate proof of concept, MSCs were genetically engineered to express a myelin oligodendrocyte glycoprotein-specific receptor. Engineered MSCs retained their immunosuppressive capacity, infiltrated into the brain upon intranasal cell administration, and were able to significantly reduce disease symptoms of experimental autoimmune encephalomyelitis (EAE). Mice treated with CNS-targeting MSCs were resistant to further EAE induction whereas non-targeted MSCs did not give such persistent effects. Histological analysis revealed increased brain restoration in engineered MSC-treated mice. In conclusion, MSCs can be genetically engineered to target the brain and prolong therapeutic efficacy in an EAE model.

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