Transplantation of galectin-1-expressing human neural stem cells into the injured spinal cord of adult common marmosets

J Neurosci Res. 2010 May 15;88(7):1394-405. doi: 10.1002/jnr.22322.

Abstract

Delayed transplantation of neural stem/progenitor cells (NS/PCs) into the injured spinal cord can promote functional recovery in adult rats and monkeys. To enhance the functional recovery after NS/PC transplantation, we focused on galectin-1, a carbohydrate-binding protein with pleiotropic roles in cell growth, differentiation, apoptosis, and neurite outgrowth. Here, to determine the combined therapeutic effect of NS/PC transplantation and galectin-1 on spinal cord injury (SCI), human NS/PCs were transfected by lentivirus with galectin-1 and green fluorescent protein (GFP), (Gal-NS/PCs) or GFP alone (GFP-NS/PCs), expanded in vitro, and then transplanted into the spinal cord of adult common marmosets, 9 days after contusive cervical SCI. The animals' motor function was evaluated by their spontaneous motor activity, bar grip power, and performance on a treadmill test. Histological analyses revealed that the grafted human NS/PCs survived and differentiated into neurons, astrocytes, and oligodendrocytes. There were significant differences in the myelinated area, corticospinal fibers, and serotonergic fibers among the Gal-NS/PC, GFP-NS/PC, vehicle-control, and sham-operated groups. The Gal-NS/PC-grafted animals showed a better performance on all the behavioral tests compared with the other groups. These findings suggest that Gal-NS/PCs have better therapeutic potential than NS/PCs for SCI in nonhuman primates and that human Gal-NS/PC transplantation might be a feasible treatment for human SCI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism
  • Callithrix / surgery*
  • Cell Differentiation / physiology
  • Disease Models, Animal
  • Female
  • Galectin 1 / genetics
  • Galectin 1 / metabolism*
  • Graft Survival / physiology
  • Green Fluorescent Proteins / genetics
  • Nerve Regeneration / physiology
  • Neurogenesis / physiology
  • Neuronal Plasticity / physiology
  • Neurons / cytology
  • Neurons / metabolism
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism
  • Paralysis / metabolism
  • Paralysis / physiopathology
  • Paralysis / surgery
  • Pyramidal Tracts / cytology
  • Pyramidal Tracts / injuries
  • Pyramidal Tracts / metabolism
  • Recovery of Function / physiology
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / surgery*
  • Stem Cell Transplantation / methods*
  • Stem Cells / metabolism*
  • Transfection / methods
  • Treatment Outcome

Substances

  • Galectin 1
  • Green Fluorescent Proteins