Multiple Sclerosis (MS) is a chronic, immune-mediated disorder marked by inflammation, demyelination, and neurodegeneration, necessitating regenerative therapies. Mesenchymal stem cell (MSC) therapy offers immunomodulatory and neuroprotective potential, but clinical evaluation is challenging.

This systematic review and meta-analysis, registered on PROSPERO (CRD420251017175) and following PRISMA 2020 guidelines, evaluated MRI’s role in assessing MSC therapy for MS. We searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library, screening 1687 records. Nine peer-reviewed clinical studies (n = 7–48 MS patients) were included. MRI modalities (e.g., T1/T2-weighted, diffusion tensor imaging) and outcomes (e.g., lesion load, remyelination) were analyzed narratively and quantitatively using Review Manager 5.1.

Conventional MRI detected short-term reductions in lesion load and inflammation, while advanced techniques showed microstructural repair, notably with intrathecal MSCs. An exploratory Meta-analysis of four studies found a significant T2 lesion volume decrease (mean difference -5.12 mm³, 95 % CI -9.65 to -0.59, P = 0.03, I²=93 %) and higher likelihood of no new T2 lesions (risk ratio 1.69, 95 % CI 1.31–2.19, P < 0.0001, I²=0 %). High heterogeneity and small sample sizes limited findings.

MRI shows promise as a biomarker for MSC therapy efficacy in MS, capturing lesion dynamics. Larger, standardized trials are needed to address methodological inconsistencies and validate findings. This study uniquely emphasizes the role of MRI—including advanced modalities—as a primary outcome measure for MSC therapy in MS, highlighting gaps in imaging standardization across studies