Stem cell therapy for stroke: mechanisms, clinical translation, and future perspectives

Stroke remains a primary global driver of death and disability. Although acute revascularization therapies (intravenous thrombolysis and mechanical thrombectomy) have advanced, their narrow therapeutic windows result in persistent neurological deficits for many survivors. This necessitates restorative treatments during the subacute and chronic phases. Consequently, stem cell therapies (SCT) have become a central strategic focus, moving beyond the early hypothesis of direct cell replacement toward modulation of the post-stroke microenvironment. This review synthesizes the mechanistic evidence for various stem cells, primarily mesenchymal stem cells and neural stem cells, and evaluates the clinical landscape, which shows reliable safety but variable efficacy. Critically, the review addresses a fundamental translational barrier: the poor post-transplantation survival of stem cells, a limitation that has become a central focus of ongoing research. The discussion further addresses the paradigm shift toward cell-free therapies (e.g., extracellular vesicles) and innovative bioengineering strategies aimed at enhancing cell potency. Realizing the full clinical potential of these therapies for stroke requires addressing persistent challenges in standardization and translation through dedicated collaborative research.