title: Intranasal delivery of central nervous system-retargeted human mesenchymal stromal cells prolongs treatment efficacy of experimental autoimmune encephalomyelitis.
abstract: 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.
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Moa
authors.initials: M
authors.lastname: Fransson
authors.forename: Elena
authors.initials: E
authors.lastname: Piras
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Joachim
authors.initials: J
authors.lastname: Burman
authors.forename: Ida
authors.initials: I
authors.lastname: Duprez
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harris
authors.forename: Katarina
authors.initials: K
authors.lastname: LeBlanc
authors.forename: Peetra U
authors.initials: PU
authors.lastname: Magnusson
authors.forename: Eva
authors.initials: E
authors.lastname: Brittebo
authors.forename: Angelica S I
authors.initials: AS
authors.lastname: Loskog
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002490:Central Nervous System / Q000166:cytology* / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000628:therapy*; D005818:Genetic Engineering; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control / Q000628:therapy; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000235:genetics / Q000378:metabolism
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein
keywords: chimeric antigen receptor; experimental autoimmune encephalitis; gene engineering; mesenchymal stromal cells; multiple sclerosis