Stem cell therapy for ischemic stroke: neuroimaging approaches and evidence from a systematic review

Purpose: Cell-based therapy is a promising approach for ischemic stroke treatment. This systematic review and meta-analysis aimed to consolidate clinical evidence on the use of neuroimaging to evaluate stem cell therapy across all stages of stroke recovery. Methods: A systematic search was conducted in 5 databases in July 2025. They were included if neuroimaging analysis, regardless of cell source, route administration or dosage were reported. The level of evidence and risk of bias were assessed using the ROB-2 or ROBINS-I tool. Imaging data from all included articles were extracted, and randomized-effect meta-analyses were performed when two or more outcomes were available for any reported imaging parameter. Results: Thirty articles were included in the systematic review, of which four were eligible for meta-analysis. Meta-analysis of subacute stroke patients revealed no significant differences in infarct volume reduction at 3 months (SMD = −0.50; 95% CI: −1.15 to 0.51; p = 0.13; I² = 63%) or 1 year (SMD = −1.02; 95% CI: −3.63 to 1.60; p = 0.45; I² = 92%) between treatment and control group. Chronic stroke patients exhibited less overall volume loss. There was a trend toward improved white matter recovery and motor cortex activity, reflected in increased DTI and fMRI parameters. SPIO-labeled autologous stem cells recently proved safe in patients, with T2* imaging showing engraftment and migration. Conclusion: Advanced neuroimaging offers a valuable non-invasive tool for assessing the effects of stem cell therapy in ischemic stroke. However, substantial heterogeneity in imaging protocols and reporting limits cross-study comparisons. Standardization of neuroimaging methodology is essential to advance future research and clinical translation.