Mesenchymal stem cells show no neuroregenerative benefit in PMS

No neuroregenerative effect of mesenchymal stem cells (MSCs) was observed in a placebo-controlled trial of participants with progressive multiple sclerosis (PMS). Initial signals of reduced brain atrophy and lower inflammatory cerebrospinal fluid protein levels at 6 months were not sustained. Moreover, local inflammatory reactions following MSC administration suggest that intrathecal MSCs in PMS should be used with caution.

MSCs have demonstrated immunomodulatory and neuroregenerative potential in MS in pre-clinical and clinical studies, although not all were placebo-controlled. A large, randomised trial previously failed to show a significant benefit [1], while intrathecal application has been considered more promising. To further evaluate this approach, the randomised, placebo-controlled, SMART-MS trial (NCT04749667) was conducted [2]. Dr Christopher Elnan Kvistad (Haukeland University Hospital, Norway) presented the results. A total of 18 PMS participants not receiving disease-modifying treatment received a single intrathecal injection of 1 million MSCs/kg body weight or saline, administered at baseline or after 6 months in a crossover design. The primary endpoint was combined evoked potentials (visual, sensory, and motor) at 6 months, before crossover. Total follow-up was 18 months.

At 6 months, no significant difference was found between groups in combined evoked potential latencies after adjusting for baseline values (β=−0.31; 95% CI −1.84 to 1.22; P=0.668). Results were similar at 12 months after adjusting for crossover (β=−0.32; 95% CI −1.26 to 0.62; P=0.476). No effects were seen on the Expanded Disability Status Scale (EDSS), 9-Hole Peg Test (9HPT), or Timed 25-Feet Walk (T25FW). A significant reduction in brain atrophy was detected at 6 months in the MSC group (β=9.37; 95% CI 0.29–18.45; P=0.044), but this effect was not sustained at 12 months. Likewise, a trend towards reduced serum glial fibrillary acidic protein was observed at 6 months (β=−16.03; 95% CI −33.0 to 0.3; P=0.054), but this trend was not sustained at 12 months. No significant effects were found on neurofilament light chain (NFL) or optical coherence tomography (OCT).

Adverse events were more frequent with MSCs, consisting mainly of local inflammatory reactions. A participant developed low back pain requiring hospitalisation, likely related to the MSC injection, which was resolved with prednisolone. Another participant developed chronic coccydynia due to arachnoiditis.

1. Uccelli A, et al. Lancet Neurol. 2021;20(11):917-929.
2. Kvistad CE, et al. Study of mesenchymal autologous stem cells as regenerative treatment for multiple sclerosis – the SMART-MS trial. O150, ECTRIMS 2025 Congress, 24–26 September 2025, Barcelona, Spain.

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Posted on 25 November 202525 November 2025