Cotransplant of neural stem cells and NT-3 gene modified Schwann cells promote the recovery of transected spinal cord injury

Spinal Cord. 2007 Jan;45(1):15-24. doi: 10.1038/sj.sc.3101943. Epub 2006 Jun 13.

Abstract

Study design: An animal model of transected spinal cord injury (SCI) was used to test the hypothesis that cografted neural stem cells (NSCs) and NT-3-SCs promote morphologic and functional recoveries of injured spinal cord.

Objective: To explore whether cotransplant of NSCs and NT-3-SCs could promote the injured spinal cord repair.

Setting: Zhongshan Medical College, Sun Yat-sen University, PR China.

Methods: Female Sprague-Dawley (SD) rats weighing on 200-220 g were used to prepare SCI models. The spinal cord was transected between T(9) and T(10), then NSCs, SCs+NSCs, LacZ-SCs+NSCs, or NT-3-SCs+NSCs were grafted into the transected site.

Results: (1) Part of NSCs could differentiate to neuron-like cells in the transected site and the percentage of differentiation was NT-3-SCs+NSCs group>SCs+NSCs group>NSCs group. (2) In the grafted groups, there were 5-HT, CGRP, and SP positive nerve fibres within the transected site. Some fluorogold (FG)-labeled cells were found in the spinal cord rostral to the transected site, the red nuclei and the inner pyramidal layer of sensorimotor cortex. (3) The cells grafted could enhance the injured neurons survival in inner pyramidal layer of sensorimotor cortex, red nuclei of midbrain, and Clark's nuclei of spinal cord's L1 segment, could decrease the latency and increase the amplitude of cortical somatosensory evoked potential (CSEP) and cortical motor evoked potential (CMEP), and could promote partly structural and functional recovery of the SCI rats.

Conclusion: These results demonstrate that cografted NT-3-SCs and NSCs is a potential therapy for SCI.

Sponsorship: This research was supported by Chinese National Key Project for Basic Research (G1999054009), Chinese National Natural Science Foundation (30270700) and Social Developmental Foundation of Guangdong Province (2003C33808) to YS Zeng; Natural Science Foundation of Guangdong Province (04300468) and Medical Science Research Grant of Guangdong Province (A2004081) to JS Guo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Count / methods
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Disease Models, Animal
  • Evoked Potentials, Motor / physiology
  • Female
  • Immunohistochemistry / methods
  • Nerve Regeneration / physiology
  • Nerve Tissue Proteins / metabolism
  • Neural Conduction / physiology
  • Neurons / physiology*
  • Neurotrophin 3 / biosynthesis
  • Neurotrophin 3 / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / physiology
  • Reaction Time / radiation effects
  • Recovery of Function
  • Schwann Cells / metabolism*
  • Schwann Cells / transplantation
  • Sciatic Nerve / physiopathology
  • Spinal Cord Injuries / surgery*
  • Stem Cell Transplantation / methods*
  • Stem Cells / physiology*
  • Stilbamidines / metabolism
  • Transfection / methods

Substances

  • 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
  • Nerve Tissue Proteins
  • Neurotrophin 3
  • Stilbamidines