Effects of human neural stem cell transplantation in canine spinal cord hemisection

Neurol Res. 2009 Nov;31(9):996-1002. doi: 10.1179/174313209X385626. Epub 2009 Jan 9.

Abstract

Objectives: Previous works have reported that the transplantation of neural stem cells (NSCs) may improve functional recovery after spinal cord injury (SCI), but these results have been mainly obtained in rat models. In the present work, the authors sought to determine whether the transplantation of human NSCs improves functional outcome in a canine SCI model and whether transplanted NSCs survive and differentiate.

Methods: Human NSCs (HB1. F3 clone) were used in this work. Lateral hemisection at the L2 level was performed in dogs and either (1) Matrigel (200 microl) alone as a growth-promoting matrix or (2) Matrigel seeded with human NSCs (10(7) cells/200 microl) were transplanted into hemisected gaps. Using a canine hind limb locomotor scale, functional outcomes were assessed over 12 weeks. Immunofluorescence staining was performed to examine cell survival, differentiation and axonal regeneration.

Results: Compared with dogs treated with Matrigel alone, dogs treated with Matrigel + human NSCs showed significantly better functional recovery (10.3 +/- 0.7 versus 15.6 +/- 0.7, respectively, at 12 weeks; p<0.05). Human nuclei-positive cells were found mainly near hemisected areas in dogs treated with Matrigel + NSCs. In addition, colocalization of human nuclei and neuronal nuclei or myelin basic protein was clearly observed. Moreover, the Matrigel + NSC group showed more ascending sensory axon regeneration.

Conclusions: The transplantation of human NSCs has beneficial effects on functional recovery after SCI, and these NSCs were found to differentiate into mature neurons and/or oligodendrocytes. These results provide baseline data for future clinical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Nuclear / metabolism
  • Biomarkers / metabolism
  • Calcitonin Gene-Related Peptide / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Nucleus / ultrastructure
  • Cells, Cultured
  • Collagen / pharmacology
  • Collagen / therapeutic use
  • Disability Evaluation
  • Disease Models, Animal
  • Dogs
  • Drug Combinations
  • Glial Fibrillary Acidic Protein / metabolism
  • Graft Survival / drug effects
  • Graft Survival / physiology
  • Growth Cones / metabolism
  • Growth Cones / ultrastructure
  • Humans
  • Laminin / pharmacology
  • Laminin / therapeutic use
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Myelin Basic Protein / metabolism
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology
  • Nerve Tissue Proteins / metabolism
  • Neurogenesis / drug effects
  • Neurogenesis / physiology
  • Proteoglycans / pharmacology
  • Proteoglycans / therapeutic use
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Spinal Cord Injuries / surgery*
  • Stem Cell Transplantation / methods*
  • Stem Cells / cytology
  • Stem Cells / physiology*
  • Treatment Outcome

Substances

  • Antigens, Nuclear
  • Biomarkers
  • Drug Combinations
  • Glial Fibrillary Acidic Protein
  • Laminin
  • Myelin Basic Protein
  • Nerve Tissue Proteins
  • Proteoglycans
  • neuronal nuclear antigen NeuN, human
  • matrigel
  • Collagen
  • Calcitonin Gene-Related Peptide