Neural Stem Cells Regenerate Relay Circuits; New Axons Formed Across Severe Spinal Cord Injury

Interesting in light of the spinal cord neural stem cell human trials being planned by Neuralstem (CUR) and currently underway by StemCells Inc. (STEM). 

In the new University research, scientists were able to regenerate “an astonishing degree” of axonal growth at the site of severe spinal cord injury in rats.  Their research revealed that early stage neurons have the ability to survive and extend axons to form new, functional neuronal relays across an injury site in the adult central nervous system (CNS).

The study also proved that at least some types of adult CNS axons can overcome a normally inhibitory growth environment to grow over long distances.  Importantly, stem cells across species exhibit these properties.

Researchers embedded neural stem cells in a matrix of fibrin -- a protein key to blood clotting already used in human neuron procedures -- mixed with growth factors to form a gel.  The gel was then applied to the injury site in rats with completely severed spinal cords.

“Using this method, after six weeks, the number of axons emerging from the injury site exceeded by 200-fold what had ever been seen before,” said Mark Tuszynski, MD, PhD, professor in the UC San Diego Department of Neurosciences and director of the UCSD Center for Neural Repair. “The axons also grew 10 times the length of axons in any previous study and, importantly, the regeneration of these axons resulted in significant functional improvement.”

In addition, adult cells above the injury site regenerated into the neural stem cells, establishing a new relay circuit that could be measured electrically. “By stimulating the spinal cord four segments above the injury and recording this electrical stimulation three segments below, we detected new relays across the transaction site,” said Tuszynski.

To confirm that the mechanism underlying recovery was due to formation of new relays, when rats recovered, their spinal cords were re-transected above the implant.  The rats lost motor function – confirming formation of new relays across the injury.

The grafting procedure resulted in significant functional improvement: On a 21-point walking scale, without treatment, the rats score was only 1.5; following the stem cell therapy, it rose to 7 – a score reflecting the animals’ ability to move all joints of affected legs.

Results were then replicated using two human stem cell lines, one already in human trials for ALS.  “We obtained the exact results using human cells as we had in the rat cells,” said Tuszynski.

Adapted from the UCSD announcement.