Summary: Intensive physical therapy in tandem with neural stem cell grafts increases tissue growth, repair, and functionality more than using the treatments alone for spinal cord injuries.
In recent years, researchers have made measurable progress, using animal models, to promote tissue regeneration in spinal cord injuries (SCI) through implanted neural stem cells or grafts.
Other efforts have shown that intensive physical rehabilitation can improve function after SCI by promoting greater or new roles for undamaged or spared cells and neural circuits.
In a new paper, published August 22, 2022 in the journal JCI Insight, researchers at University of California San Diego School of Medicine address the question of whether rehabilitation can augment functional outcomes when combined with pro-regenerative therapies, such as stem cell grafting.
Using a rat model, researchers induced a cervical lesion that impaired the animals’ ability to grasp with its forelimbs. There were four groups: animals who underwent the lesion alone; animals who received a subsequent grafting of neural stem cells designed to grow and connect with existing nerves; animals who received rehabilitation only; and animals who received both stem cell therapy and rehabilitation.
Rehabilitation therapy for some animals began one month after initial injury, a time point that approximates when most human patients are admitted to SCI rehabilitation centers. Rehabilitation consisted of daily activities that rewarded them with food pellets if they performed grasping skills.
The researchers found that rehabilitation enhanced regeneration of injured corticospinal axons at the lesion site in rats, and that a combination of rehabilitation and grafting produced significant recovery in forelimb grasping when both treatments occurred one month after injury.
“These new findings indicate that rehabilitation plays a critically important role in amplifying functional recovery when combined with a pro-regenerative therapy, such as a neural stem cell transplant,” said first author Paul Lu, PhD, associate adjunct professor of neuroscience at UC San Diego School of Medicine and research health science specialist at the Veterans Administration San Diego Healthcare System.
“Indeed, we found a surprisingly potent benefit of intensive physical rehabilitation when administered as a daily regimen that substantially exceeds what humans are now provided after SCI.”
Senior author Mark H. Tuszynski, MD, PhD, professor of neurosciences and director of the Translational Neuroscience Institute at UC San Diego School of Medicine, and colleagues have long worked to address the complex challenges of repairing SCIs and restoring function.
In 2020, for example, they reported on the observed benefits of neural stem cell grafts in mice and in 2019, described 3D-printed implantable scaffolding that would promote nerve cell growth.
Spinal cord injuries remain a largely unresolved medical challenge. Nearly 18,000 people in the United States suffer SCIs each year, with another 294,000 persons living with an SCI, usually involving some degree of permanent paralysis or diminished physical function, such as bladder control or difficulty breathing.
“There is a great unmet need to improve regenerative therapies after SCI,” said Tuszynski.
“We hope that our findings point the way to a new potential combination treatment consisting of neural stem cell grafts plus rehabilitation, a strategy that we hope to move to human clinical trials over the next two years.”
Co-authors include: Camila Marques De Freria, Lori Graham, Amanda N. Tran and Dena Yassin, all at UC San Diego; Ashley Villarta, Veterans Administration Medical Center, San Diego; J. Russell Huie and Adam R. Ferguson, UC San Francisco.
About this genetics and spinal cord injury research news
Author: Scott La Fee
Contact: Scott La Fee – UCSD
Image: The image is credited to Thomas Deerinck, UC San Diego
Original Research: Open access.
“Rehabilitation combined with neural progenitor cell grafts enables functional recovery in chronic spinal cord injury” by Paul Lu et al. JCI Insight
Rehabilitation combined with neural progenitor cell grafts enables functional recovery in chronic spinal cord injury
We reported previously that neural progenitor cell (NPC) grafts form neural relays across sites of subacute spinal cord injury (SCI) and support functional recovery.
Here, we examine whether NPC grafts after chronic delays also support recovery and whether intensive rehabilitation further enhances recovery.
One month after severe bilateral cervical contusion, rats received daily intensive rehabilitation, NPC grafts, or both rehabilitation and grafts.
Notably, only the combination of rehabilitation and grafting significantly improved functional recovery. Moreover, improved functional outcomes were associated with a rehabilitation-induced increase in host corticospinal axon regeneration into grafts.
These findings identify a critical and synergistic role of rehabilitation and neural stem cell therapy in driving neural plasticity to support functional recovery after chronic and severe SCI.