title: Transplanted Peripheral Blood Stem Cells Mobilized by Granulocyte Colony-Stimulating Factor Promoted Hindlimb Functional Recovery After Spinal Cord Injury in Mice.
abstract: Granulocyte colony-stimulating factor (G-CSF) mobilizes peripheral blood stem cells (PBSCs) derived from bone marrow. We hypothesized that intraspinal transplantation of PBSCs mobilized by G-CSF could promote functional recovery after spinal cord injury. Spinal cords of adult nonobese diabetes/severe immunodeficiency mice were injured using an Infinite Horizon impactor (60 kdyn). One week after the injury, 3.0 µl of G-CSF-mobilized human mononuclear cells (MNCs; 0.5 × 10(5)/µl), G-CSF-mobilized human CD34-positive PBSCs (CD34; 0.5 × 10(5)/µl), or normal saline was injected to the lesion epicenter. We performed immunohistochemistry. Locomotor recovery was assessed by Basso Mouse Scale. The number of transplanted human cells decreased according to the time course. The CD31-positive area was significantly larger in the MNC and CD34 groups compared with the vehicle group. The number of serotonin-positive fibers was significantly larger in the MNC and CD34 groups than in the vehicle group. Immunohistochemistry revealed that the number of apoptotic oligodendrocytes was significantly smaller in cell-transplanted groups, and the areas of demyelination in the MNC- and CD34-transplanted mice were smaller than that in the vehicle group, indicating that cell transplantation suppressed oligodendrocyte apoptosis and demyelination. Both the MNC and CD34 groups showed significantly better hindlimb functional recovery compared with the vehicle group. There was no significant difference between the two types of transplanted cells. Intraspinal transplantation of G-CSF-mobilized MNCs or CD34-positive cells promoted angiogenesis, serotonergic fiber regeneration/sparing, and preservation of myelin, resulting in improved hindlimb function after spinal cord injury in comparison with vehicle-treated control mice. Transplantation of G-CSF-mobilized PBSCs has advantages for treatment of spinal cord injury in the ethical and immunological viewpoints, although further exploration is needed to move forward to clinical application.
authors.affiliation: Department of Orthopaedic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masao
authors.initials: M
authors.lastname: Koda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Takeo
authors.initials: T
authors.lastname: Furuya
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sakuma
authors.forename: Kei
authors.initials: K
authors.lastname: Kato
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okawa
authors.forename: Taigo
authors.initials: T
authors.lastname: Inada
authors.forename: Koshiro
authors.initials: K
authors.lastname: Kamiya
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Ota
authors.forename: Satoshi
authors.initials: S
authors.lastname: Maki
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Chikato
authors.initials: C
authors.lastname: Mannoji
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006614:Hindlimb / Q000503:physiopathology; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009186:Myelin Sheath / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000628:therapy*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor