Human Mesenchymal stromal cells expressing a CNS-targeting receptor can be administrated intra nasally and cure expersimental autoimmune enchphlomyelitis
(English)Manuscript (preprint) (Other academic)
Mesenchymal stromal cells (MSCs) are a heterogeneous population of stromal cells residing in most connective tissues and have the capacity to suppress effector cells of the immune system. In experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, systemic treatments with both murine and human MSCs have proven beneficial because of their capacity to suppress overt immune reactions. However, systemic administration of such cells may cause problems with infectious disease and low numbers of cells that reach the inflamed tissue. We hypothesized that MSCs can be accumulated and retained in the CNS using gene transfer of a CNS-targeting device and intranasal cell delivery. In the current investigation, MSCs were engineered to express a myelin oligodendrocyte glycoprotein (MOG)-specific receptor using lentiviral vectors. Genetically engineered MSCs retained their suppressive capacity in vitro and successfully targeted the brain upon both intraperitoneal and intranasal delivery. Engineered MSCs cured mice from disease symptoms and these mice were resistant to further EAE challenge. Encephalitic T cells isolated from cured mice displayed an anergic profile while peripheral T cells were still responsive to stimuli. Further, MSC treatment reduced the level of inflammatory cytokines in the brain and implyed reduced damage to axons. In conclusion, MSCs can be genetically engineered to target CNS and efficiently suppress encephalomyelitis in an active EAE model upon intranasal delivery.
MSC, CAR, CNS, intranasal delivery, EAE
Immunology in the medical area
Research subject Medical Science
IdentifiersURN: urn:nbn:se:uu:diva-132746OAI: oai:DiVA.org:uu-132746DiVA: diva2:359062