Nogo receptor-Fc delivered by haematopoietic cells enhances neurorepair in a multiple sclerosis model.

Autor:	Ye S; Department of Neuroscience, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia., Theotokis P; B', Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, Stilponos Kiriakides str. 1, 54636 Thessaloniki, Macedonia, Greece., Lee JY; ToolGen Inc., Gangseo-gu, 07789 Seoul, Korea., Kim MJ; Department of Neuroscience, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia., Nheu D; Department of Neuroscience, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia., Ellen O; Department of Neuroscience, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia., Bedford T; Department of Neuroscience, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia., Ramanujam P; Department of Neuroscience, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia., Wright DK; Department of Neuroscience, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia., McDonald SJ; Department of Neuroscience, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia., Alrehaili A; Department of Neuroscience, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia.; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, PO Box 11099, Taif 21944, Saudi Arabia., Bakhuraysah M; Department of Neuroscience, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia.; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, PO Box 11099, Taif 21944, Saudi Arabia., Kang JH; Department of Neuroscience, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia., Siatskas C; STEMCELL Technologies Inc., Vancouver, British Columbia V6A 1B6, Canada., Tremblay CS; Australian Centre for Blood Diseases, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia., Curtis DJ; Australian Centre for Blood Diseases, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia.; Clinical Haematology, Alfred Hospital, Prahran, Victoria 3004, Australia., Grigoriadis N; B', Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, Stilponos Kiriakides str. 1, 54636 Thessaloniki, Macedonia, Greece., Monif M; Department of Neuroscience, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia., Strittmatter SM; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06536, USA., Petratos S; Department of Neuroscience, Central Clinical School, Monash University, Prahran, Victoria 3004, Australia.
Jazyk:	angličtina
Zdroj:	Brain communications [Brain Commun] 2023 Apr 04; Vol. 5 (2), pp. fcad108. Date of Electronic Publication: 2023 Apr 04 (Print Publication: 2023).
DOI:	10.1093/braincomms/fcad108
Abstrakt:	Nogo receptor 1 is the high affinity receptor for the potent myelin-associated inhibitory factors that make up part of the inflammatory extracellular milieu during experimental autoimmune encephalomyelitis. Signalling through the Nogo receptor 1 complex has been shown to be associated with axonal degeneration in an animal model of multiple sclerosis, and neuronal deletion of this receptor homologue, in a disease specific manner, is associated with preserving axons even in the context of neuroinflammation. The local delivery of Nogo receptor(1-310)-Fc, a therapeutic fusion protein, has been successfully applied as a treatment in animal models of spinal cord injury and glaucoma. As multiple sclerosis and experimental autoimmune encephalomyelitis exhibit large numbers of inflammatory cell infiltrates within the CNS lesions, we utilized transplantable haematopoietic stem cells as a cellular delivery method of the Nogo receptor(1-310)-Fc fusion protein. We identified CNS-infiltrating macrophages as the predominant immune-positive cell type that overexpressed myc-tagged Nogo receptor(1-310)-Fc fusion protein at the peak stage of experimental autoimmune encephalomyelitis. These differentiated phagocytes were predominant during the extensive demyelination and axonal damage, which are associated with the engulfment of the protein complex of Nogo receptor(1-310)-Fc binding to myelin ligands. Importantly, mice transplanted with haematopoietic stem cells transduced with the lentiviral vector carrying Nogo receptor(1-310)-Fc and recovered from the peak of neurological decline during experimental autoimmune encephalomyelitis, exhibiting axonal regeneration and eventual remyelination in the white matter tracts. There were no immunomodulatory effects of the transplanted, genetically modified haematopoietic stem cells on immune cell lineages of recipient female mice induced with experimental autoimmune encephalomyelitis. We propose that cellular delivery of Nogo receptor(1-310)-Fc fusion protein through genetically modified haematopoietic stem cells can modulate multifocal experimental autoimmune encephalomyelitis lesions and potentiate neurological recovery. Competing Interests: All other authors listed declare no competing financial and/or non-financial interests in relation to the work described. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
Databáze:	MEDLINE
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