Intranasal Delivery of CNS-Retargeted Human Mesenchymal Stromal Cells Prolongs Treatment Efficacy of Experimental Autoimmune Encephalomyelitis
2014 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 142, no 3, 431-441 p.Article in journal (Refereed) Published
Treatment with mesenchymal stromal cells (MSC) is currently of interest for a number of diseases including multiple sclerosis (MS). MSCs is well known to target inflamed tissues however, in a therapeutic scenery, systemic administration will lead to few cells reaching the brain. We hypothesized that MSCs may target the brain upon intranasal (i.n) administration and persist in CNS tissue if expressing a CNS-targeting receptor. To demonstrate proof of concept, MSCs were genetically engineered to express a myelin oligodendrocyte glycoprotein (MOG)-specific receptor. Engineered MSCs retained their immunosuppressive capacity, infiltrated into the brain upon i.n. cell administration, and were able to significantly reduce disease symptoms of experimental autoimmune encephalomyelitis (EAE). The mice treated with CNS-targeting MSCs were resistant to further EAE induction whereas non-targeted MSC 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.
Place, publisher, year, edition, pages
2014. Vol. 142, no 3, 431-441 p.
IdentifiersURN: urn:nbn:se:uu:diva-223631DOI: 10.1111/imm.12275ISI: 000337600500012PubMedID: 24588452OAI: oai:DiVA.org:uu-223631DiVA: diva2:713489
De två första författarna delar förstaförfattarskapet.2014-04-232014-04-232015-03-11Bibliographically approved