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 patients with progressive MS (PMS). Initial signals of reduced brain atrophy and lower inflammatory cerebrospinal fluid (CSF) 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 preclinical 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. 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 (CEPs: 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 CEP 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 on the Expanded Disability Status Scale (EDSS), 9-Hole Peg Test (9-HPT), or Timed 25-Feet Walk (T25-FW). A signal of reduced 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 toward reduced serum glial fibrillary acidic protein (GFAP) 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.

Adverse events were more frequent with MSCs, mainly 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. Kvistad CE, et al. Front Neurol. 2022;13:891514.
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.

Medical writing support was provided by Michiel Tent.

Copyright ©2025 Medicom Medical Publishers



Posted on 30 September 2025