title: Treatment of spinal cord injury by an advanced cell transplantation technology using brain-derived neurotrophic factor-transfected mesenchymal stem cell spheroids.
abstract: Curing spinal cord injury (SCI) is challenging because of the onset of multiple and irreversible pathological responses to such injury. To suppress the responses, we employed an advanced cell transplantation technology integrating three-dimensional spheroid cell transplantation with non-viral gene transfection using biodegradable polycations. Brain-derived neurotrophic factor (BDNF)-transfected mesenchymal stem cell (MSC) spheroids were transplanted at thoraces level (Th9) to SCI region in mice. BDNF-transfected MSC spheroid transplantation led to a significantly enhanced recovery of hindlimb motor function in acute phase of SCI with myelinated axons preserved at the SCI region, while use of either technology in isolation, BDNF transfection or spheroid culture, exerted only a limited therapeutic effect, demonstrating the importance of integrated approaches. Secretion of endogenous therapeutic proteins, such as anti-inflammatory factors, was greater in MSC spheroids than in monolayer culture MSCs, and these factors appeared to act synergistically alongside BDNF secretion in SCI treatment. This study forms a basis for cell therapy regulating complex pathophysiologic processes.
authors.affiliation: Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for the Persons with Disabilities, Saitama, Japan; Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hayakawa
authors.affiliation: Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for the Persons with Disabilities, Saitama, Japan; Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ogata
authors.affiliation: Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Japan.
authors.forename: Sakae
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan. Electronic address: kataoka@bmw.t.u-tokyo.ac.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Sensory & Motor System Medicine, Faculty of Medicine, The University of Tokyo, Japan. Electronic address: itaka-ort@umin.net.
authors.forename: Keiji
authors.initials: K
authors.lastname: Itaka
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D006614:Hindlimb; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration; D020127:Recovery of Function; D018874:Spheroids, Cellular / Q000378:metabolism / Q000637:transplantation*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D014162:Transfection
chemical_list: D000893:Anti-Inflammatory Agents; D019208:Brain-Derived Neurotrophic Factor
keywords: Biodegradable polycation; Cell transplantation; Non-viral gene transfection; Spheroid; Spinal cord injury