Mesenchymal stem cells therapy for Ischaemic stroke: Mechanism and progress

Ischaemic stroke is a leading global cause of death and long-term disability. Current acute interventions, notably thrombolysis and mechanical thrombectomy, are limited by narrow therapeutic windows and primarily focus on vascular recanalization. These approaches often fail to address the sustained neurovascular injury, persistent inflammation, and insufficient endogenous repair that underlie long-term functional impairment. In this context, mesenchymal stem cells (MSCs) have emerged as a highly promising regenerative strategy for ischemic stroke, targeting the multifaceted pathophysiology beyond acute revascularization. Sourced predominantly from bone marrow, umbilical cord, and adipose tissue, MSCs exert effects primarily through their multimodal paracrine actions. They home to the injury site and orchestrate the local immune microenvironment by dampening excessive inflammation and promoting a shift in macrophages toward a pro-repair phenotype. Furthermore, MSCs enhance neurovascular plasticity and tissue regeneration through the release of bioactive factors and extracellular vesicles. This review provides a comprehensive analysis of MSCs sources and their multimodal mechanisms of action, synthesizes preclinical evidence and clinical trial advancements in stroke, discusses persisting translational challenges, and outlines future directions in the field. Collectively, MSCs-based therapies represent a transformative approach with significant potential to bridge a critical gap in stroke care, advancing the goal of long-term tissue regeneration and meaningful functional recovery.