title: Intravenous infusion of mesenchymal stem cells promotes functional recovery in a model of chronic spinal cord injury.
abstract: Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow improves behavioral function in rat models of spinal cord injury (SCI). However, most studies have focused on the acute or subacute phase of SCI. In the present study, MSCs derived from bone marrow of rats were intravenously infused 10weeks after the induction of a severe contusive SCI. Open field locomotor function was assessed weekly until 20weeks post-SCI. Motor recovery was greater in the MSC-treated group with rapid improvement beginning in earlier post-infusion times than in the vehicle-treated group. Blood spinal cord barrier (BSCB) integrity was assessed by the intravenous infusion of Evans Blue (EvB) with spectrophotometric quantitation of its leakage into the parenchyma. In MSC-treated rats, BSCB leakage was reduced. Immunohistochemical staining for RECA-1 and PDGFR-β showed increased microvasculature/repair-neovascularization in MSC-treated rats. There was extensive remyelination around the lesion center and increased sprouting of the corticospinal tract and serotonergic fibers after MSC infusion. These results indicate that the systemic infusion of MSCs results in functional improvement that is associated with structural changes in the chronically injured spinal cord including stabilization of the BSCB, axonal sprouting/regeneration and remyelination.
authors: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
authors: Tomonori
authors: T
authors: Morita
authors: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA. Electronic address: msasaki@sapmed.ac.jp.
authors: Masanori
authors: M
authors: Sasaki
authors: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors: Yuko
authors: Y
authors: Kataoka-Sasaki
authors: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors: Masahito
authors: M
authors: Nakazaki
authors: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors: Hiroshi
authors: H
authors: Nagahama
authors: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors: Shinichi
authors: S
authors: Oka
authors: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
authors: Tsutomu
authors: T
authors: Oshigiri
authors: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
authors: Tsuneo
authors: T
authors: Takebayashi
authors: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
authors: Toshihiko
authors: T
authors: Yamashita
authors: Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
authors: Jeffery D
authors: JD
authors: Kocsis
authors: Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA; Center for Neuroscience and Regeneration Research, VA Connecticut Healthcare System, West Haven, CT 06516, USA.
authors: Osamu
authors: O
authors: Honmou
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation / Q000379:methods; D002908:Chronic Disease; D004195:Disease Models, Animal; D007262:Infusions, Intravenous / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009043:Motor Activity / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology
keywords: mesenchymal stem cell; spinal cord injury; transplantation