Cellular Therapies

Cellular therapy is a relatively new treatment option, which contributes to significant advancements in technology and genetic research (Vaquero et al. 2017). Cell transplantation with mesenchymal stromal cells via injection into the site of the syrinx shows potential in the future treatment of syringomyelia without surgery (Vaquero et al. 2017).

Author Year; Country
Research Design
Score
Total Sample Size

Methods Outcome

Vaquero et al. 2018a; Spain
Pre-Post
N=6

Population: Mean age: 39 yr; Gender: Males=6; Injury etiology: SCI-trauma=6; Mean time since injury: 13.7 yr; Level of severity: AISA-A=3, AISA-B=2, AISA-D=1; Lesion location: D5=2, D3=1, D4=1, D8=1, L1=1.
Intervention: Cell therapy medicament (NC1, PEI number 12-141), developed by the Spanish Agency of Medicament and Health Products. The solution was injected into the syrinx over the course of one month.
Outcome Measures: Alteration to genome of expanded cells, ASIA, SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS), Visual Analog Scale (VAS), Penn and modified Ashworth scale (MAS), Geffner scale, and neurogenic bowel dysfunction scale (NBD).
  1. No genome alterations were detected during the cell expansion process.
  2. Pin prick scores on the ASIA measure improved (p=0.06), this effect was only observed at 6 mo follow-up.
  3. Scores on the IANR-SCIFRS (spinal cord function) increased at 3 mo follow-up (p=0.06), and 6 mo follow-up (p=0.06).
  4. There were no significant differences in VAS score post-injection (p=0.25), although patients self-reported a decrease in neuropathic pain.
  5. There were no significant differences in levels of spasticity or spasms experienced by patients post-injection (MAS, p=0.50).
  6. The Geffner scale (bladder dysfunction) showed no significant differences post-injection (p=0.25).
  7. The NBD scale showed no significant differences post-injection (p=0.12), although four patients observed an improvement.

Oraee-Yazdani et al. 2021; Iran
Pre-Post
N=11

Population: Mean age: 29.09±9.41 yr; Gender: males=9, females=2; Level of injury: cervical=4, thoracic=7; Severity of injury: ASIA A=11; Time since injury: ≥ 3 and ≤ 12 mo.
Intervention: The patients received an intrathecal autologous combination of Mesenchymal stem cell (MSCs) and Schwann cells (SCs); and were followed up for 12 months.
Outcome Measures: American Spinal Injury Association’s (ASIA) sensory-motor scale, spinal cord independence measure (SCIM- III), subjective changes and adverse events (AE) (assessed by a checklist developed by the authors); electromyography (EMG), nerve conduction velocity (NCV), magnetic resonance imaging (MRI), and urodynamic study (UDS) were conducted for all the patients at the baseline, 6 mo, and 1 yr post-intervention. 
  1. Light touch AIS score alterations were approximately the same as the pinprick changes (11.6 ± 13.1 and 12 ± 13, respectively) in 50% of the cervical and 63% of the lumbar-thoracic patients, and both were more than the motor score alterations (9.5 ± 3.3 in 75% of the cervical and 14% of the lumbar-thoracic patients).
  2. SCIM III total scores (21.2 ± 13.3) and all its sub-scores (“respiration and sphincter management” (15 ± 9.9), “mobility” (9.5 ± 13.3), and “self-care” (6 ± 1.4)) had statistically significant  changes after cell injection (ps<0.05). 
  3. The most notable positive, subjective
    improvements were in trunk movement, equilibrium in standing/sitting position, the sensation of the bladder and rectal filling, and the ability of voluntary voiding.
  4. Safety evaluation revealed no systemic complications, and radiological images showed no neoplastic overgrowth, syringomyelia, or pseudo- meningocele. 

Discussion

To our knowledge, only one study has examined the use of cellular therapies for the treatment of syringomyelia. Vaquero et al. (2018) had a small patient sample of six, however they were able to observe strong improvements in spinal cord function at three and six months post-injection. Unfortunately, in terms of outcomes measuring bladder and bowel dysfunction no significant differences were reported. More studies are required on the use of cellular therapy as a potential non-surgical treatment for syringomyelia before any substantial conclusions can be drawn.

Cellular therapies have been used to improve various functional outcomes in individuals with SCI (Oraee-Yazdani et al. 2021). A recent study by Oraee-Yazdani and colleagues (2021) assessed the safety of intrathecal co-transplantation of autologous bone marrow mesenchymal and schwann cells in patients with subacute traumatic complete SCI. Radiological images revealed no presence of syringomyelia at 6- month and 12-month post-intervention.

Conclusions

There is level 4 evidence (from one pre-post study: Vaquero et al., 2018a) that mesenchymal stromal cell therapy may be effective in improving spinal cord function post-SCI.

There is level 4 evidence (from one pre-post study: Oraee-Yazdani et al. 2021) that intrathecal co-transplantation of autologous bone marrow mesenchymal and schwann cells does not result in adverse events, such as syringomyelia, in individuals with subacute traumatic complete SCI.