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Neuroscience. 2016 Oct 29;335:221-31. doi: 10.1016/j.neuroscience.2016.08.037. Epub 2016 Aug 30.

Intravenous infusion of mesenchymal stem cells promotes functional recovery in a model of chronic spinal cord injury.

Author information

1
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.
2
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.
3
Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
4
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
5
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.
6
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.

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.

KEYWORDS:

mesenchymal stem cell; spinal cord injury; transplantation

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