Comparative efficacy and safety of seven stem cell therapies for ischemic stroke: an updated network meta-analysis

Cell-based therapies represent a promising treatment for ischemic stroke, but the comparative efficacy and safety profiles among stem cell types have not been systematically compared. This network meta-analysis evaluates different stem cell therapies for ischemic stroke. We conducted a literature search using PubMed, the Cochrane Library, and Web of Science up to May 2025. The primary efficacy outcomes included the National Institutes of Health Stroke Scale, the modified Rankin Scale, the Barthel Index, the Fugl-Meyer Assessment, and infarct volume. Safety outcomes included serious adverse events and mortality. Eighteen randomized controlled trials involving 1,006 patients assessed seven stem cell therapies. Peripheral blood stem cells ranked highest for neurological recovery. Bone marrow-derived ALDHbr cells best improved daily living, while bone marrow mononuclear cells enhanced motor function. Mesenchymal stem cells reduced infarct volume most. Endothelial progenitor cells showed the lowest serious adverse events and ranked highest in mortality reduction, although the latter did not reach statistical significance. Mesenchymal stem cells were the only stem cell type that significantly reduced mortality. In conclusion, peripheral blood stem cells excelled in neurological recovery, bone marrow-derived ALDHbr cells and bone marrow mononuclear cells in functional outcomes, and endothelial progenitor cells in lowest serious adverse events, with mesenchymal stem cells being the only stem cell type that significantly reduced mortality. Further large-scale randomized controlled trials are needed to confirm optimal dosing and timing.