Multiroute Administration of Wharton's Jelly Mesenchymal Stem Cells in Chronic Complete Spinal Cord Injury: A Phase I Safety and Feasibility Study

Major Points and Findings:

This Turkish phase I study gave donor umbilical cord (Wharton’s jelly) mesenchymal stem cells to six people with chronic, complete thoracic spinal cord injury, using three routes at every session (intrathecal, intravenous and intramuscular). Repeated dosing of cord-derived cells by intrathecal and intravenous routes is also how this clinic works, so the safety record is directly relevant.

The efficacy figures are large. They come from six patients with no control group and no restriction on other treatments, and the report contains several internal inconsistencies. It is summarised here for its procedural and safety detail and should not be relied on as evidence of benefit. The authors themselves say the improvements “cannot be solely attributed” to the cells.

Aim:

To assess the safety and preliminary efficacy of allogeneic Wharton’s jelly MSCs (WJ-MSCs), given by three routes at once, in adults with chronic complete spinal cord injury.

Methods:

Open-label, single-arm phase I study, described as multicentre and approved by the Turkish Ministry of Health. No trial registry number is given in the paper.

Inclusion criteria: Age 18 or over; radiologically confirmed chronic injury (at least 6 months old); severe disability (wheelchair-bound and needing assistance); no meaningful functional improvement for at least 3 months; no cancer or organ failure; life expectancy over 12 months.

Exclusion criteria: Significant medical or psychiatric illness; recent meningitis, sepsis or other severe infection; uncontrolled seizures; a CNS tumour or any cancer in the past five years; white cell count of 15,000 or more, platelets of 100,000 or fewer; liver enzymes above three times or creatinine above 1.5 times the upper limit of normal; previous participation in a stem cell trial.

The participants were six people (five men, one woman) aged 19 to 39. All had thoracic burst fractures between T5 and T12. Two injuries were from firearms, two from traffic accidents, one from a fall and one from skiing. Time from injury to first treatment was 6 months in one, 9 months in two, 12 months in one, 4 years in one and 12 years in one. Three had had only physiotherapy beforehand and three had had spinal surgery. The baseline lower-limb motor score averaged 1.67 out of 50, which fits a complete injury, although individual AIS grades are not tabulated.

The umbilical cords came from full-term births with donor consent and were processed in a GMP facility. Tissue pieces were cultured until cells migrated out, and cells were harvested at passage 3. Release tests required viability above 90%, standard MSC surface markers, a normal karyotype, negative mycoplasma and endotoxin below 0.0625 EU/mL.

Treatment was given in four rounds, at the start, week 1, week 4 and week 6. In every round each patient received 1 million cells per kg by each of three routes: intrathecally by lumbar puncture in 3 mL, intravenously in 30 mL over 30 minutes, and intramuscularly in 20 mL under ultrasound guidance. The total was 3 million cells per kg per round and 12 million per kg overall. Patients had to be fit for sedation or general anaesthesia. Each session was followed by one day of monitoring in intensive care and then transfer to a neurosurgery ward for physiotherapy. Other drugs and rehabilitation were unrestricted throughout the year of follow-up.

Outcome measures were the Functional Independence Measure (FIM), Modified Ashworth spasticity scale, ASIA motor and sensory scores, the Wexner bowel incontinence score and the Qualiveen short form for urinary quality of life.

Results:

Safety: No serious adverse events occurred in 12 months. No infection, allergic reaction, anaesthetic complication, rise in CRP or white cells, new neuropathic pain, neurological deterioration or tumour was recorded. The per-session table shows:

• Fever (low grade) in 4 of 6 patients, after 7 of the 24 treatment sessions, controlled with standard antipyretics
• Pain or muscle soreness in 2 of 6, after 4 sessions
• Headache in 2 of 6, after 4 sessions

All settled within 24 hours. The text attributes the headaches to the intramuscular injections. Because a lumbar puncture was performed in the same session, that attribution is hard to verify.

Function: All figures are group means for six people, before treatment and at 12 months.

• FIM motor score: 42.50 to 56.17, significant from month 1 onward
• ASIA lower-limb motor score: 1.67 to 15.00, no change at week 1 or month 1, significant from month 2
• Light touch: 62.00 to 81.67. Pin prick: 62.00 to 81.33. Both significant from month 2
• Spasticity (Modified Ashworth total per leg): right leg 8.00 to 2.17, left leg 7.83 to 2.17
• FIM cognitive score: unchanged, as expected
• Bowel score: 20 to 17, described as a 15% improvement. Urinary quality of life: improved by 10.9%

The standard deviation of the motor score at 12 months (11.23 on a mean of 15.00) shows the gain was very uneven between patients, but individual results are not reported. No patient-level AIS grade conversions are given.

The report is not internally consistent. The discussion gives the 12-month motor score as 12.00, which is the 6-month value in the results table. The table gives 15.00. The abstract says cells were given “twice monthly for 2 months” while the schedule table lists weeks 0, 1, 4 and 6. The text refers to a 4-month assessment where the tables show month 6. This summary follows the tables.

Conclusions:

The authors conclude that repeated triple-route WJ-MSC treatment was safe and feasible at 1 million cells per kg per route, with only minor, short-lived reactions. On efficacy the conclusion is more careful than the results section. The authors write that without a control group, and with drug treatment and rehabilitation left uncontrolled, “the observed improvements cannot be definitively attributed to WJ-MSCs alone”. They call for larger controlled trials.

Background Information:

Three of the six participants were treated 6 to 9 months after injury, a window in which some recovery can still occur without any cell therapy, and all were moved to a ward for ongoing physiotherapy. A randomised, placebo-controlled trial of intrathecal WJ-MSCs published in 2026 found that people given placebo improved their motor scores as much as people given cells. Gains of the kind reported here therefore need a comparison group before they can be credited to the treatment.

The rationale given for using three routes is intrathecal delivery for the cord itself, intravenous delivery for a body-wide immune effect and intramuscular delivery to target the end organ. The design cannot separate the contribution of any one route.

The authors attribute any effect to substances the cells release (growth factors such as BDNF and VEGF, anti-inflammatory signals and extracellular vesicles). They do not propose that the cells turn into nerve tissue.