IMS researchers discover how the spine could heal itself after injury using hidden stem cells

Institute of Medical Science researchers have discovered a promising new way the body could heal itself after spinal cord injury by harnessing the power of hidden stem cells.

The preclinical study, published in Nature Neuroscience, represents what researchers Laureen Hachem and Michael Fehlings say is potentially a huge breakthrough in the field of regenerative neuroscience.

The research is the result of Hachem’s PhD thesis, which she did under the supervision of Fehlings and Charles Tator, both professors of neurosurgery at the University of Toronto’s Temerty Faculty of Medicine and internationally recognized pioneers in spinal cord injury research. 

The findings show, for the first time, that a population of stem cells deep inside the adult spinal cord — derived from ependymal cells — can be activated therapeutically to enhance recovery following injury.

Normally these cells lie dormant and briefly “wake up” after injury — temporarily gaining stem-cell like properties. But they don’t stay active long enough to make a significant difference in repairing damage.

“One of the big challenges that limits recovery after severe neurological injuries is that, unlike in lower-level invertebrates, the human central nervous system loses the ability to regenerate” explains Fehlings, who is also vice chair of research in Temerty Medicine’s department of surgery and co-director of its spine program.

Hachem’s interest in studying spinal cord injuries goes back to when she first joined Tator’s lab as a high school student. This is also when she first met Fehlings, a clinician-scientist and himself a former PhD student of Tator's.

“The question that’s been driving scientists for decades is how can we harness what’s already inside the body to support recovery?” says Hachem, a trainee in U of T’s surgeon-scientist training program currently finishing her final year of neurosurgery residency.

The researchers wanted to find a way to keep these healing ependymal cells active longer. They discovered that a brain chemical called glutamate — released in excessive levels after trauma — can activate these cells through a specific type of receptor called AMPA receptors.

They tested a drug called CX546, which boosts AMPA receptor activity, to see if it would help.

A range of benefits emerged. The drug kept the healing cells active longer, helped the cells move toward the injury site, enhanced electrical activity in the spinal circuits, and improved communication between the cells, which is important for healing.

Not only did the mice treated with the drug recover better, but they also moved more easily.

When AMPARs were genetically disabled, the drug no longer worked, confirming that its effects depend on these receptors.

While this work is still in the early days, it is an important step toward new therapeutic treatments that could improve recovery for people with spinal cord damage and other neurological injuries.

“What Laureen has shown in this study could unlock the key to endogenous regeneration in the human spinal cord” says Fehlings, who is also a neurosurgeon and scientist at Toronto Western Hospital’s Krembil Brain Institute. “Ultimately, the hope is that this proof of concept can be translated into a clinical trial.”

Fehlings is confident that these findings, together with other promising research from his lab, will advance the standard of care and quality of patients’ lives. He is happy to see the torch being passed on to the next generation of clinician-scientists.

Hachem recently received the Governor General’s Gold Medal — one of Canada's most prestigious honours for graduate students — in recognition of her academic excellence. She is also the recipient of this year's Siminovitch Salter Award from IMS for outstanding scholarly contributions in the PhD program. 

Hachem will soon be starting a fellowship in complex and minimally invasive spine surgery at the University of Miami. She is eager to continue exploring the “interesting questions and promising avenues of research” her graduate studies have unearthed, and to further the ongoing pursuit of a proven treatment for spinal cord injuries.