[Spinal Cord Injury Phase 1] Long-term Follow-up Results of Intraspinal Administration of Autologous Bone Marrow-Derived Mesenchymal Stem Cells in Patients with Spinal Cord Injury

Study Summary

Study Results

We directly injected mesenchymal stem cells cultured from the patients’ own bone marrow into the spinal cords of 10 patients with quadriplegia resulting from traumatic cervical spinal cord injury. The evaluation criteria included arm muscle strength grades, the size of the cavity (cavity) within the spinal cord as observed on magnetic resonance imaging (MRI), electrophysiological testing, and activities of daily living.

At the 6-month mark, arm muscle strength improved in 6 of the 10 patients, and among them, 3 showed improvements in activities of daily living. Follow-up of these 3 patients through 30 to 39 months revealed that they were able to perform tasks such as preparing meals or lifting a cup while wearing an arm brace. MRI scans showed that the syringomyelia walls had disappeared in 2 patients by 32 months, and all 3 patients showed improved electrophysiological test results. Among the remaining 7 patients, 2 also showed some improvement in muscle strength at 55 and 62 months.

No permanent complications occurred. One patient experienced moderate paresthesia for 10 months after administration, but it resolved spontaneously. Follow-up MRI scans showed no signs of syringomyelia or tumors, and CT scans revealed no ectopic calcification. One patient died of pneumonia three years after administration.

Figure. Changes in the size of the spinal cord cavity in Patient 1 (preoperative → 36 months)

Study Design

This was a study conducted at a single tertiary general hospital in Korea that observed only the treatment group without a control group. Ten patients who had developed complete motor paralysis due to traumatic cervical spinal cord injury at least one month prior participated. Regarding the ASIA classification, which indicates the severity of injury, four patients were classified as Grade A (complete loss of sensation and motor function) and six as Grade B (partial sensory function remaining).

In a previous study, all 10 patients were followed for 6 months; this study conducted long-term follow-up on 3 of them who showed improvement in activities of daily living. All three had an ASIA grade of B, and the time elapsed from injury to surgery was 8 months, 38 months, and 96 months, respectively. The remaining 7 patients did not undergo regular evaluations after 6 months.

Cells Used and Injection Method

Autologous bone marrow-derived mesenchymal stem cells, harvested from the patients’ own iliac crests, were cultured in a GMP facility for 4 weeks up to the fifth passage. The release criteria were a survival rate of 90% or higher, negative for microbial contamination, at least 90% of cells positive for CD73 and CD105, and less than 3% of cells positive for CD14, CD34, and CD45.

After removing the posterior bony structure of the spine and incising the dura mater, 8 × 10⁶ cells were injected in divided doses using a 26.5-gauge needle at two sites above the spinal canal and three sites within the canal, and the injection sites were covered with fibrin glue. While closing the dura mater, 4 × 10⁷ cells were introduced into the subarachnoid space, and an additional 5 × 10⁷ cells were administered via lumbar puncture at 4 and 8 weeks, respectively.

Discussion

These results are based on observations lasting up to 39 months following the direct injection of autologous bone marrow-derived mesenchymal stem cells into the injured spinal cord. Citing previous reports that natural recovery typically ceases after 12 months, the research team explained that the continued improvement in muscle strength observed in two patients beyond that point may be related to the cell administration.

The researchers explained that the disappearance of the cavity wall observed on MRI might indicate that the cells reduced scarring.

There are clear limitations. Since there was no control group and only three participants were included in the long-term follow-up, statistical analysis could not be performed. Of the remaining seven participants, four had their conditions assessed only through outpatient visits or by telephone. Given that all three patients who showed improvement in activities of daily living had an ASIA grade of B, the researchers noted that the treatment may be more suitable for patients with residual nerve function. The clinical significance of the MRI changes has not yet been confirmed. The cells used in this study were manufactured at Pamcell’s GMP facility, and the research was funded by the National Research Foundation of Korea.