title: Neuroprotective and growth-promoting effects of bone marrow stromal cells after cervical spinal cord injury in adult rats.
abstract: OBJECTIVE
  Bone marrow stromal cells (BMSC) have been shown to provide neuroprotection after transplantation into the injured central nervous system. The present study investigated whether adult rat BMSC differentiated along a Schwann cell lineage could increase production of trophic factors and support neuronal survival and axonal regeneration after transplantation into the injured spinal cord.
  
  
  METHODS
  After cervical C4 hemi-section, 5-bromo-2-deoxyuridine (BrdU)/green fluorescent protein (GFP)-labeled BMSC were injected into the lateral funiculus at 1 mm rostral and caudal to the lesion site. Spinal cords were analyzed 2-13 weeks after transplantation.
  
  
  CONCLUSIONS
  Treatment of native BMSC with Schwann cell-differentiating factors significantly increased production of brain-derived neurotrophic factor in vitro. Transplanted undifferentiated and differentiated BMSC remained at the injection sites, and in the trauma zone were often associated with neurofilament-positive fibers and increased levels of vascular endothelial growth factor. BMSC promoted extensive in-growth of serotonin-positive raphaespinal axons and calcitonin gene-related peptide (CGRP)-positive dorsal root sensory axons into the trauma zone, and significantly attenuated astroglial and microglial cell reactions, but induced aberrant sprouting of CGRP-immunoreactive axons in Rexed's lamina III. Differentiated BMSC provided neuroprotection for axotomized rubrospinal neurons and increased the density of rubrospinal axons in the dorsolateral funiculus rostral to the injury site. The present results suggest that BMSC induced along the Schwann cell lineage increase expression of trophic factors and have neuroprotective and growth-promoting effects after spinal cord injury.
authors.affiliation: Department of Integrative Medical Biology, Section of Anatomy, Umeå University, Umeå, Sweden. liudmila.novikova@anatomy.umu.se
authors.forename: Liudmila N
authors.initials: LN
authors.lastname: Novikova
authors.forename: Maria
authors.initials: M
authors.lastname: Brohlin
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kingham
authors.forename: Lev N
authors.initials: LN
authors.lastname: Novikov
authors.forename: Mikael
authors.initials: M
authors.lastname: Wiberg
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000379:methods*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002574:Cervical Vertebrae / Q000293:injuries; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009416:Nerve Regeneration; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018696:Neuroprotective Agents; D020933:Neurotrophin 3 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012012:Red Nucleus / Q000166:cytology / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology*; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D049452:Green Fluorescent Proteins; D015740:Calcitonin Gene-Related Peptide