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Cell transplantation aids spinal cord repair in rats

BMJ 2000; 320 doi: (Published 11 March 2000) Cite this as: BMJ 2000;320:670
  1. Xavier Bosch
  1. Barcelona

    A team of Spanish researchers has shown that transplantation of a specific type of glial cell in rats that became paraplegic after their spinal cords had been completely severed promotes functional recovery and regeneration of motor axons over a long distance (Neuron 2000;25:425-35).

    “This constitutes a dramatic functional improvement and anatomical repair after complete severance of the adult mammalian spinal cord,” said lead researcher Dr Almudena Ramón-Cueto of the Centro de Biología Molecular Severo Ochoa in Madrid, Spain.

    “Our results open doors in the search for a therapeutic procedure that might be useful in humans with spinal cord injuries and central nervous system trauma,” she added.

    The olfactory ensheathing glia (OEG) is a unique type of glial cell contained in the adult mammalian olfactory bulb. Unlike other cells of the central nervous system OEG promotes axonal growth. OEG was obtained from purified cultures from primary olfactory bulb.

    Surgical procedures were performed on adult Wistar rats. The spinal cord was transected at the T8-T9 thoracic segment in 21 rats, and OEG was injected into the spinal cord of 9 rats near the transection site. A group of 12 rats was injured but not injected.

    Transection caused flaccid paralysis of both hindlimbs immediately after injury in all animals. After transection and transplantation, recovery of voluntary movement of the hindlimb was assessed using a climbing test that had four different levels of difficulty.

    All animals had been previously trained to climb onto inclined grids. On reaching the top of the grid, the animals had to completely pass their forelimbs and hindlimbs onto a platform to be classed as succeeding in performing the manoeuvre.

    Seven months after transection there was no improvement among the rats that had not had an injection of OEG. However, all of the rats that had been injected with OEG showed a highly significant recovery of motor function. The rats that had been injected could voluntarily move their hindlimbs; they also had plantar placement of the paw and could support their body weight. They also recovered sensorimotor reflexes.

    Eight months after surgery the regeneration of motor axons was studied by cutting the spinal cord longitudinally. Consecutive sections of the spinal cord were collected onto different slides. Whereas all of the spinal cords from rats that had received OEG had evidence of some structural repair at macroscopic and microscopic levels, this repair was absent in the spinal cords taken from rats who had not been injected with OEG. In rats that had been treated, axonal regeneration was observed through the distal spinal cord.

    Dr Ramón-Cueto said that OEG can be obtained from adult donors and thus offers the possibility of autologous transplantation. Treating spinal cord injury in humans to promote axonal regeneration and functional recovery is still a clinical challenge.

    However, the researchers concluded that “on the basis of our results, the next challenge is to analyse if OEG would succeed in promoting functional and structural recovery of the lesioned spinal cord of primates; this, in turn, would determine to what extent our technique could also be applicable to humans.”

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