Study: foetal stem cells repair spinal cord injury in rats

Posted: May 30, 2013 at 1:45 pm

A study has been published showing how injecting foetal neural cells into the damaged spinal cords of rats led to a marked regeneration of the neural pathways.

According to a team from the University of California, San Diego School of Medicine and colleagues in the Czech Republic, the Netherlands and Slovakia, once cells extracted from the foetal spinal cord were grafted on to the damaged region, links between the injected cells and existing ones developed and debilitating muscle spasms subsided.

"The primary benefits were improvement in the positioning and control of paws during walking tests and suppression of muscle spasticity," said Martin Marsala, a professor in UC San Diego's department of Anesthesiology and coauthor on the paper, published in the Stem Cell Research and Therapy journal online. "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."

The rats were injured three days prior to treatment, with a circular rod used to compress the L3 vertebra for 15 minutes. Damage to the L3 is associated most commonly with herniated discs and is a hot spot for chronic back pain in humans. Mice that received the graft also received immunosuppressants for the duration (they died two months later, in a "planned sacrifice") and the grafts were stained with immunofluorescence so it was clear where the original tissue began and ended. The subjects were then monitored for any improvements in movement -- noting things like gait and ability to climb ladders -- and frequency of muscle spasms during computer-controlled ankle rotations.

Although there wasn't any improvement of note when it came to things like the ladder climbing test, muscle spasms did significantly subside, normal heat and pain sensitivities returned and the rats appeared to have better control over their paws. Perhaps more significantly, the team came away with physical evidence of the regeneration with MRI scans picking up the immunofluorescent stem cell grafts and showing how they had filled the hole in the spinal region left by the rod damage, with the "development of putative GABA-ergic synapses between grafted and host neurons".

Although the study provided significant results, the team ultimately wants to opt-out of using embryonic spinal stem cells. This is not because of the inevitable moral questions that arise from using foetal cells, but because in an ideal world we don't want to be administering immunosuppressants -- the only way of avoiding that is to use cells produced by our own bodies. This could be achieved by using pluripotent stem cells from patients, then turning them into neural precursors. Making sure these cells are stable enough to insert into a human spinal cord is key to the therapy being taken forward, but there are already plans to take the study up a notch with human trials involving patients with injuries between T2 and T12 that have no motor or sensory functions below the injury. It's also already being done elsewhere in the world.

StemCells Inc has been using human neural stem cells derived from adult tissue -- known as HuCNS-SC cells (an engineered cell devised by the company) -- in small trials on patients suffering from severe spinal cord injuries. After six months, sensory functions had begun to return in two of the three patients involved in the trial, with those improvements persisting for the duration of the year-long trial.

"Between the six- and 12-month evaluations, one patient converted from a complete to an incomplete injury," said Armin Curt, professor at the Spinal Cord Injury Centre at Balgrist University Hospital in Zurich, where the trial took place. "While much more clinical research needs to be done to demonstrate efficacy, the types of changes we are observing are unexpected and very encouraging given that these are patients in the chronic stage of complete spinal injury."

Unlike the rat study, the Zurich trial is not however a controlled clinical study and took in just those three patients. Nevertheless, the results are astounding and show great promise for using a patient's own cells one day in the future.

Elsewhere this week, a team at the University of Wisconsin-Madison School of Veterinary Medicine has announced it has managed to induce improved muscle function in rats with a model of terminal motor neurone disease ALS, using adult stem cells from human bone marrow. The cells were once again engineered to fulfill a specific function -- in this case the team wanted them to promote regrowth of damaged nerve cells and targeted the point where the nerve meets the muscle (where degeneration commonly begins). The cells would not become neurons, but release growth factors.

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Study: foetal stem cells repair spinal cord injury in rats

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