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Review
. 2025 Jun 29;17(6):e86988.
doi: 10.7759/cureus.86988. eCollection 2025 Jun.

Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Multiple Sclerosis: A Systematic Review

Maysaa N Amin  1 , Rahma Hashish  2 , Khaled Agha Tabari  3 , Shivling S Swami  4 , Alousious Kasagga  5 , Amanuel Kefyalew Assefa  6 , Ann Kashmer Yu  4
Affiliations
Review

Immunomodulatory Role of Mesenchymal Stem Cell Therapy in Multiple Sclerosis: A Systematic Review

Maysaa N Amin et al. Cureus. .

Abstract

The progressive immune-mediated disease known as multiple sclerosis (MS) is characterized by myelin degradation, inflammation, and neurodegeneration. Recent research has examined the potential of mesenchymal stem cell (MSC) therapy for treatment, focusing on its neuroprotective and immunomodulatory properties. This study looked at how MSC transplantation affects cerebrospinal fluid (CSF) biomarkers and the immune system, and checked whether they can indicate the safety and effectiveness of the treatment for MS. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this systematic review was conducted. The final selection comprised eight studies: two randomized controlled trials (RCTs), two non-randomized experimental studies, three systematic reviews with meta-analyses, and one narrative review. Following MSC therapy in MS patients, significant alterations in neuroprotective biomarker levels were found in the CSF, exhibiting positive results. Immunologically, MSC therapy facilitated the expansion of regulatory T cells (Tregs) and suppressed T helper type 17 (Th17) cell activity, restoring immune balance and diminishing neuroinflammation. Clinically, improvements in Expanded Disability Status Scale (EDSS) scores and MRI lesion burden were observed in a significant subset of patients. Across the included studies, MSC therapy was generally safe, with mild, self-limiting adverse effects. However, heterogeneity in MSC sources, administration routes, and outcome measures, along with small sample sizes, limited comparability. In conclusion, MSC-based therapies show promising potential as a personalized approach to MS management.

Keywords: biomarkers; cerebrospinal fluid; immunomodulation; mesenchymal stem cell; multiple sclerosis.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. Flowchart showing the article selection process.
AMSTAR 2, Assessment of Multiple Systematic Reviews 2; SANRA 2, Scale for the Assessment of Narrative Review Articles 2; JBI, Joanna Briggs Institute
Figure 2
Figure 2. Alterations in CSF biomarkers following MSC transplantation.
MSC, Mesenchymal Stem Cell; CSF, Cerebrospinal Fluid; NF-L, Neurofilament Light Chains; VEGF-A, Vascular Endothelial Growth Factor A; HGF, Hepatocyte Growth Factor; NCAM-1, Neural Cell Adhesion Molecule 1; LIF, Leukemia Inhibitory Factor; MCP-1, Monocyte Chemoattractant Protein-1; SDF-1, Stromal Cell-Derived Factor 1; CXCL13, CXC Motif Chemokine Ligand 13; MMP-9, Matrix Metalloproteinase-9; CCL2, Chemokine Ligand 2
Figure 3
Figure 3. Immunomodulatory mechanism of mesenchymal stem cell therapy.
MSC, Mesenchymal Stem Cell; Treg, Regulatory T Cells; NK, Natural Killer Cells; Th17, T Helper 17
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