4.5 Article

Transplantation of Galectin-1-Expressing Human Neural Stem Cells Into the Injured Spinal Cord of Adult Common Marmosets

Journal

JOURNAL OF NEUROSCIENCE RESEARCH
Volume 88, Issue 7, Pages 1394-1405

Publisher

WILEY
DOI: 10.1002/jnr.22322

Keywords

spinal cord injury; galectin-1; common marmoset; neural stem/progenitor cells; preclinical study

Categories

Funding

  1. Japanese Ministry of Education, Sports and Culture
  2. Human Frontier Science Program Organization
  3. Core Research for Evolutional Science and Technology (CREST) from the Japan Science and Technology Corporation (JST)
  4. General Insurance Association of Japan
  5. High-Tech Research Center in a Private University in Japan
  6. Keio University
  7. Ministry of Education, Culture, Sports, Science and Technology, Japan

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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. (C) 2010 Wiley-Liss, Inc.

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