Findings Point to Possible Major Therapeutic Intervention for Chronic Spinal Cord Injuries Via Stem Cell Injections
Lead author Ivan Cheng, MD and Michael G. Fehlings, MD, PhD Comment
Injection of human neural stem cells distally, but not locally, to the site of chronic spinal cord injury lead to significant functional recovery in a rat model, researchers reported in the June issue of The Spine Journal.
"To our knowledge, this is the first study to demonstrate a significant functional improvement after application of neural stem cells in a model of chronic spinal cord injury," said lead author Ivan Cheng, MD, Associate Professor in the Department of Orthopaedic Surgery at Stanford University Medical Center in Stanford, CA. "Similar to other studies, the local injection of cells at the site of the chronic spinal cord injury did not result in a significant change. The distal transplantation of cells away from the site of injury through intrathecal injection, however, led to significant locomotor improvement."
"I applaud the authors for an interesting study that showed promising initial results," commented Michael G. Fehlings, MD, PhD, who is Professor of Neurosurgery and Co-Director of the Spine Program at the University of Toronto in Ontario. "This study adds to the growing body of evidence that stems cells can enhance functional recovery after spinal cord injury."
Rats Were Treated 4 Weeks After Injury
The investigators randomized 24 adult female Long-Evans hooded rats with experimental spinal cord injury into 4 groups: 2 experimental groups received injection of human neural stem cells (hNSCs) locally at the injury site or through a separate distal laminotomy; and 2 control groups received control media injection either locally or distally. Injections were given 4 weeks postinjury in all groups.
At 10 weeks following injection, rats that received distal hNSCs injection showed significantly greater improvement in function compared to the group that received distal injection of control cell media (mean Basso, Beattie, and Bresnahan (BBB) locomotor scores, 11.3 vs 5.8; P=0.035). Rats that received local hNSCs injection showed improved function scores, but the improvement was not significantly different from control rats given local injection of contrast medium (mean BBB scores, 11.3 vs 5.8; P=0.37).
The overall change in BBB score from the time of injection to follow-up ranged from a high of +5.8 with distal hNSC injection to a low of −1.1 with local injection of contrast medium.
Importance of the Distal Approach to Injection of Neural Stem Cells
Dr. Fehlings noted that his laboratory also uses distal injection of neural stem cells, rather than local injection.
"The lesion site itself is felt to be not the most optimal for the survival of the cells," Dr. Fehlings explained. "There is a cavity in the area of injury, and inhibitory factors expressed in the lesion. Neural stem cells have developmental properties that allow them to migrate, particularly in the white matter niche. By transplanting neural stems cells in a healthier area, it enhances the likelihood of survival and integration. This does appear to be the optimal strategy."
What Does 4 Week Postinjury in Rats Equate to in Humans?
The investigators took an interesting approach in delaying transplantation until 4 weeks after the injury, Dr. Fehlings said. Most animal studies initiate transplantation at 2 weeks postinjury, "the thought being that it makes sense to avoid the postinjury phase because acute spinal cord lesions release factors that contribute to secondary injury," Dr. Fehlings noted.
He added that 6-weeks postinjury in the rodent is estimated to represent a 6-month time frame in humans, which is the beginning of the chronic phase of spinal cord injury. Thus, the 4-week time point may be "somewhere between the late subacute phase into the earliest chronic phase of injury. This becomes important because it is important to not overread the results of the study to suggest that this [procedure] is necessarily going to work in patients who have injuries of long standing duration."
"Nonetheless, the paper adds to the growing body of evidence, and points to some areas that require further research," Dr. Fehlings said. "Studies examining the long-term survival of the cells, the integration of the cells into the host tissue, and the effects on the host tissue are of interest. I applaud the authors for an interesting study that showed promising initial results."
Study Provides Findings For Translational Use
"This study provides exciting findings for translational use," Dr. Cheng told SpineUniverse. "First, it provides a potentially major therapeutic intervention to patients with chronic spinal cord injuries who have few options. Even if we can effect a change in these patients' spasticity and/or bladder/bowel function, it would make an enormous difference in their quality of life.
"Second, the intrathecal injection of neural stem cells through a lumbar puncture is a relatively simple intervention for the patient," Dr. Cheng said. "There is no need for an open surgical procedure, and injections can potentially be provided in the office or outpatient setting with minimal morbidity. While further work is needed to determine the mechanism by which these stem cells act, we are excited to provide a new avenue of hope for significant improvement in the lives of chronic spinal cord injured patients.
In terms of future research, "We are currently studying the histology of the spinal cords from the cohort of animals in our published paper as well as further analyzing the behavior of labeled neural stem cells via in vivo bioluminescence imaging with more frequent time intervals," Dr. Cheng said. "Intermediate-term plans include a phase I/IIa clinical trial to determine the safety, tolerability, and efficacy of injecting neural stem cells via lumbar puncture in patients with chronic spinal cord injury."