Mesenchymal Stem Cell Therapy for Ischemic Stroke: Bridging Clinical Evidence and Translational Challenges

Ischemic stroke remains a major cause of long-term disability worldwide. Despite advances in acute reperfusion therapies, many survivors experience persistent neurological deficits due to irreversible neuronal loss and limited endogenous repair, highlighting the need for effective regenerative strategies. Mesenchymal stem cells (MSCs) have emerged as promising candidates for cell-based therapy because of their multimodal paracrine effects, including immunomodulation, promotion of angiogenesis and neurogenesis, attenuation of neuroinflammation, and enhancement of endogenous neuroplasticity. This Concise Review synthesizes the current clinical evidence supporting MSC therapy for ischemic stroke, critically examines the biological and translational determinants of therapeutic efficacy, and discusses emerging strategies, including engineered MSCs, extracellular vesicle (EV)-based therapies, and integration with neurorehabilitation. A structured literature search of PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library through June 2026 prioritized randomized controlled trials, systematic reviews, and meta-analyses. The largest contemporary meta-analysis, encompassing 30 clinical studies and 1,217 participants, confirmed the favorable safety profile of MSC therapy while emphasizing the need for larger, standardized randomized trials to establish definitive clinical efficacy. Available evidence indicates that MSC therapy is generally safe, with serious treatment-related adverse events being uncommon, and may improve neurological impairment and functional recovery. However, heterogeneity in cell source, manufacturing protocols, administration route, treatment timing, dosing strategies, and patient selection continues to limit definitive conclusions regarding efficacy. Future progress will depend on standardized Good Manufacturing Practice-compliant manufacturing, validated potency assays, optimized patient selection, identification of the optimal therapeutic window, and integration of engineered MSCs, EV-based therapies, and combination approaches with neuromodulation.