Highlights:

  • Neural stem cell (NSC) transplants demonstrated long-term safety with no tumor formation or immune rejection in patients with chronic spinal cord injuries (SCI).
  • NSC transplants enhanced voluntary motor control and sensory perception in two out of four patients, with some regaining partial muscle function.
  • The treatment reduced chronic neuropathic pain in two patients, though functional independence improvements were not observed.

Whether through a car accident, a fall, or a sports injury, spinal cord injuries (SCI) remain among the most devastating medical conditions, often resulting in permanent loss of motor and sensory function. While traditional treatments focus on stabilization and rehabilitation, scientists have yet to reverse nerve damage resulting from SCI successfully. Now, a groundbreaking phase 1 clinical trial, published in Cell Reports Medicine, has demonstrated the long-term safety and therapeutic potential of neural stem cell (NSC) therapy for promoting neurological recovery in patients with spinal cord injuries.

Researchers from the University of California, San Diego, conducted a five-year follow-up study involving four patients with chronic thoracic SCI. The results demonstrate the safety of NSC transplantation using the NSI-566 cell line and reveal early but significant neurophysiological improvements.

Rewiring the Body: Neural Stem Cells and SCI

Neural stem cells (NSCs) are specialized cells capable of differentiating into neurons, astrocytes, and oligodendrocytes — critical cell types for nerve repair. This study used NSI-566, a human spinal cord-derived NSC line developed from an eight-week-old fetal spinal cord, ethically obtained under FDA and NIH guidelines. These cells were chosen for their ability to promote neural repair without tumor formation, as seen in preclinical models. 

The phase 1 trial enrolled four patients with chronic thoracic SCI (T2-T12) classified as AIS-A, indicating complete motor and sensory loss below the injury site. Each participant received bilateral intraspinal injections of NSI-566 cells directly into the lesion site. Additionally, the patients were monitored over five years with assessments including MRI, diffusion tensor imaging (DTI), electromyography (EMG), and standard clinical metrics such as the International Standards for Neurological Classification of SCI (ISNCSCI).

Neural Stem Cell Transplants are Safe and Effective

The primary objective of the trial was to assess the safety and feasibility of the procedure. Over the five-year follow-up period, the study’s investigators reported no severe complications directly related to the treatment. Notably, among 65 recorded adverse events, only one serious case occurred. The patient developed sepsis; however, the investigators determined it to be unrelated to the stem cell therapy, confirming the treatment’s safety.

To further assess the safety of NSCs, the trial’s researchers utilized several advanced imaging techniques to analyze the injection site. Accordingly, imaging revealed no structural abnormalities, tumor formation, or immune rejection across the five-year observation period, reaffirming the treatment’s safety. 

Following treatment, two of the four participants showed measurable improvements in motor and sensory function as confirmed by ISNCSCI scores. Electromyography (EMG) tests revealed new activity in previously dormant muscle groups, suggesting the transplanted cells contributed to neural recovery. One patient developed new voluntary control over abdominal and lower back muscles, while another showed enhanced responsiveness in the lower limbs. 

In addition to these neurological improvements, two participants reported reduced pain levels. Pain reduction is a critical quality-of-life improvement for SCI patients, who often grapple with chronic discomfort or neuropathic pain. 

However, despite these promising neurological gains, they did not translate into significant functional improvements such as increased mobility or independence, highlighting the need for further research to optimize treatment strategies and dosage for enhanced patient outcomes. 

Neural Stem Cell Therapy and Aging

The ability of the body to repair nerve damage declines with age, making treatments like neural stem cell therapy particularly promising for older adults. Aging populations often face increased vulnerability to chronic pain, with up to 25% of older adults experiencing persistent pain. Additionally, neuropathic pain is common among spinal cord injury patients, which can significantly impact how one goes through life. 

The reduction in chronic neuropathic pain observed in this trial suggests that NSC therapy may offer important quality-of-life improvements for older individuals. Furthermore, the ability of NSCs to promote neural repair could be particularly beneficial in addressing age-related declines in nerve regeneration.

The Need for Future Trials   

Collectively, this trial’s results demonstrate the long-term safety of NSC transplantation. Although full functional recovery was not observed in the study’s subjects, the results highlight the potential for NSC therapy to reduce pain, promote nerve repair, and improve the quality of life for individuals with chronic spinal cord injuries.

With that said, it is still too early to draw any definitive conclusions, especially since the trial only included four subjects with no control group. Thus, to elucidate the full benefits of NSC transplantation, researchers will need to conduct larger, controlled trials. What’s more, future trials should investigate whether higher doses of NSCs or earlier intervention following injury could enhance functional outcomes. By continually optimizing the study’s design, NSC therapy advances closer to becoming a viable treatment for the more than 20 million people living with spinal cord injuries worldwide.