Mesenchymal Stem Cell Infusion Does Not Cure Multiple Sclerosis
Mesenchymal stem cell (MSC) infusion is not an effective treatment for curing or even significantly modifying the course of Multiple Sclerosis, and should not be used outside of research protocols. The highest quality evidence from the 2021 MESEMS phase 2 randomized controlled trial definitively demonstrated that bone marrow-derived MSC treatment failed to reduce inflammatory activity in active MS, with no significant effect on gadolinium-enhancing lesions (rate ratio 0.94,95% CI 0.58-1.50; p=0.78) 1.
Why MSCs Do Not Work for MS
The MESEMS trial, the largest and most rigorous study to date, conclusively showed that MSC therapy does not affect acute inflammation in MS. This multicenter, double-blind, placebo-controlled crossover trial enrolled 144 patients with active relapsing-remitting or progressive MS and found no therapeutic benefit on MRI markers of disease activity at 24 weeks 1.
- The study was specifically designed to test whether MSCs could reduce inflammatory lesions, which is the primary pathological mechanism in active MS 1
- Despite theoretical immunomodulatory and neuroprotective properties demonstrated in animal models, these effects did not translate to meaningful clinical benefit in humans 1
- The trial's conclusion explicitly states: "this study does not support the use of bone marrow-derived MSCs to treat active multiple sclerosis" 1
Safety Concerns with MSC Infusion
MSC infusions carry significant safety risks that are often underappreciated, particularly thrombotic complications from instant blood-mediated inflammatory reaction (IBMIR). Different tissue sources of MSCs express varying levels of tissue factor, which triggers the clotting cascade upon intravascular delivery 2.
- Umbilical cord-derived MSCs have caused documented venous thrombosis requiring warfarin and urokinase thrombolytic therapy 2
- Adipose tissue-derived MSCs exhibit highly procoagulant activity with reports of peripheral microthrombosis, pulmonary embolisms, and suspected deaths 2
- Even bone marrow-derived MSCs, which have the lowest thrombogenic potential, trigger IBMIR responses that vary based on donor tissue type and processing methods 2
Limited and Conflicting Clinical Data
The small uncontrolled studies that suggested potential benefit are methodologically weak and contradicted by higher-quality evidence. A 2020 systematic review identified only 10 manuscripts (7 uncontrolled trials, 2 randomized trials, and 1 case report), with highly variable and inconclusive results 3.
- In uncontrolled trials, only 48 patients improved while 16 worsened and 39 remained stable on EDSS scores—hardly compelling evidence for efficacy 3
- A 2012 open-label study of 25 patients showed that only 4 improved, 6 deteriorated, and 12 had no change in EDSS scores at 12 months 4
- A 2019 phase I study of 7 patients showed initial stability at 12 weeks, but 3 of 5 patients had declined by 48 weeks, suggesting any benefit is transient at best 5
The Proven Alternative: Autologous Hematopoietic Stem Cell Transplantation
For patients with highly active MS refractory to high-efficacy disease-modifying therapies, autologous hematopoietic stem cell transplantation (AHSCT)—not MSC infusion—is the evidence-based escalation therapy. AHSCT achieves 87% progression-free survival at 10 years in optimal candidates 2, 6.
- AHSCT is recommended by ECTRIMS and EBMT for patients meeting specific criteria: age <45 years, disease duration <10 years, EDSS <4.0, high focal inflammation on MRI, and failure of ≥1 high-efficacy DMT 2, 6
- AHSCT works through complete immune system ablation and reconstitution, a fundamentally different mechanism than the proposed immunomodulation of MSCs 2
- For young patients (<45 years) with early secondary progressive MS of short duration and documented inflammatory activity, AHSCT may be considered, but MSC therapy has no established role 2, 6
Critical Pitfall to Avoid
Do not confuse AHSCT (hematopoietic stem cells) with MSC therapy (mesenchymal stem cells)—these are completely different treatments with vastly different evidence bases. AHSCT involves bone marrow or peripheral blood stem cells that reconstitute the immune system after chemotherapy-based conditioning, while MSCs are stromal cells proposed to have immunomodulatory effects without immune ablation 2.
Current Standard of Care
Patients with active relapsing-remitting MS should receive high-efficacy disease-modifying therapies (ocrelizumab, ofatumumab, natalizumab, alemtuzumab, or cladribine) as initial treatment. Early aggressive treatment with these FDA-approved agents yields superior long-term outcomes compared to experimental therapies like MSC infusion 6, 7, 8.
- For primary progressive MS, ocrelizumab is the only FDA-approved DMT, though efficacy is limited to slowing disability progression 6, 8
- MSC therapy should only be considered within properly designed clinical trials specifically investigating tissue repair mechanisms, not as a treatment option in routine clinical practice 1