title: Cell-Based Delivery of Interleukin-13 Directs Alternative Activation of Macrophages Resulting in Improved Functional Outcome after Spinal Cord Injury.
abstract: The therapeutic effects of mesenchymal stem cell (MSC) transplantation following spinal cord injury (SCI) to date have been limited. Therefore, we aimed to enhance the immunomodulatory properties of MSCs via continuous secretion of the anti-inflammatory cytokine interleukin-13 (IL-13). By using MSCs as carriers of IL-13 (MSC/IL-13), we investigated their therapeutic potential, compared with non-engineered MSCs, in a mouse model of SCI. We show that transplanted MSC/IL-13 significantly improve functional recovery following SCI, and also decrease lesion size and demyelinated area by more than 40%. Further histological analyses in CX3CR1EGFP/+CCR2RFP/+transgenic mice indicated that MSC/IL-13 significantly decrease the number of resident microglia and increase the number of alternatively activated macrophages. In addition, the number of macrophage-axon contacts in MSC/IL-13-treated mice was decreased by 50%, suggesting a reduction in axonal dieback. Our data provide evidence that transplantation of MSC/IL-13 leads to improved functional and histopathological recovery in a mouse model of SCI.
authors.affiliation: Department of Morphology, Biomedical Research Institute, Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium; Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Wilrijk, 2610 Antwerp, Belgium.
authors.forename: Dearbhaile
authors.initials: D
authors.lastname: Dooley
authors.affiliation: Department of Morphology, Biomedical Research Institute, Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium.
authors.forename: Evi
authors.initials: E
authors.lastname: Lemmens
authors.affiliation: Department of Morphology, Biomedical Research Institute, Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: Vangansewinkel
authors.affiliation: Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Wilrijk, 2610 Antwerp, Belgium.
authors.forename: Debbie
authors.initials: D
authors.lastname: Le Blon
authors.affiliation: Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Wilrijk, 2610 Antwerp, Belgium.
authors.forename: Chloé
authors.initials: C
authors.lastname: Hoornaert
authors.affiliation: Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Wilrijk, 2610 Antwerp, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Ponsaerts
authors.affiliation: Department of Morphology, Biomedical Research Institute, Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium. Electronic address: sven.hendrix@uhasselt.be.
authors.forename: Sven
authors.initials: S
authors.lastname: Hendrix
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002452:Cell Count; D003711:Demyelinating Diseases / Q000473:pathology / Q000503:physiopathology; D018793:Interleukin-13 / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000276:immunology / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D018793:Interleukin-13; D018696:Neuroprotective Agents
keywords: cell transplantation; interleukin-13; macrophages; mesenchymal stem cells; microglia; spinal cord injury