Tuesday, 28 May 2013

Neural stem cells repair spinal cord injuries in rats

Each and every year, about 12,000 people sustain an Acute Spinal Cord injury (SCI), in the U.S. alone. SCI is a common cause of permanent disability, with symptoms varying from simple muscle weakness to total loss of voluntary muscle movement in the chest, arms, and/or legs. At the moment, there is no way to repair a damaged spinal cord, however researchers are continuously seeking new methods to induce spinal cord regeneration. Yesterday, a collaborative team of researchers, led by scientists at the University of California, San Diego School of Medicine reported that a single injection containing human neural stem cells may be enough to partially repair a SCI and improve overall function in SCI victims.

Martin Marsala, corresponding author and specialist in spinal cord traumas, said that neural stem cells harvested from a human fetal spinal cord have a therapeutic effect once transplanted on mice with spinal cord injuries. This effect ranges from less muscle spasticity to new neural connections made between the injected stem cells and the surviving neurons.

"The primary benefits were improvement in the positioning and control of paws during walking tests and suppression of muscle spasticity," said Marsala.


Spinal cord
A spinal cord injury may have debilitating effects


Human neural stem cells (hNSCs), seem to "vigorously" graft at the injury site, said Marsala.

"In all cell-grafted animals, there was robust engraftment, and neuronal maturation of grafted human neurons was noted. Importantly, cysts or cavities that can form in or around spinal injuries were not present in any cell-treated animal. The injury-caused cavity was completely filled by grafted cells." explained Marsala.

The researchers experimented on three-month-old female rats which first received an L3 spinal compression injury. Three days after the injury, the animals were randomised into three groups, receiving injections containing one of the following:
  • hNSCs
  • Placebo treatment
  • No injections at all


The hNSCs used in the study were recently approved for Phase 1 human trials in patients with chronic traumatic spinal injuries while all rats received immunosuppressive drugs to suppress any immune response to the human stem cells.

"Treatment led to a progressive and significant improvement in lower extremity paw placement, amelioration of spasticity, and normalization in thermal and tactile pain/escape thresholds at eight weeks post-grafting." an extract from the study.

According to Marsala, grafting stem cells at any time following the injury, seems to block the formation of spinal injury cavities, adding that more research is needed to determine how timing affects functional neurological benefit.

"Grafted spinal stem cells are rich source of different growth factors which can have a neuroprotective effect and can promote sprouting of nerve fibres of the host neurons. We have also demonstrated that grafted neurons can develop contacts with the host neurons and, to some extent, restore the connectivity between centres, above and below the injury, which are involved in motor and sensory processing." said Marsala.

Marsala says his team ultimate goal is to derive neural stem cells from induced pluripotent stem cells developed from the patients themselves, thus eliminating any need to use immunosuppressive drugs during the treatment.

"This is exciting, especially because, historically, there has been very little to offer patients with acute spinal cord injury" commented co-author of the study Joseph Ciacci. Ciacci said that a small phase 1 trial is under way, with the purpose to test the safety and efficacy of neural stem cells on human patients with thoracic spinal cord injuries (between vertebrae T2-T12) who have little or no motor or sensory function at or below the site of injury.

If the upcoming trial is successful, the same protocol for neural regeneration might be expanded to patients suffering from other forms of spinal cord injury, said Ciacci.

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Reference
van Gorp, S., Leerink, M., Kakinohana, O., Platoshyn, O., Santucci, C., Galik, J., Joosten, E., Hruska-Plochan, M., Goldberg, D., Marsala, S., Johe, K., Ciacci, J., & Marsala, M. (2013). Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation Stem Cell Research & Therapy, 4 (5) DOI: 10.1186/scrt209

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