Human Stem Cell-Derived Extracellular Vesicles: A Pioneering Path from Biogenesis to Cerebral Ischemic Stroke Therapy

Despite advances in modern medicine and increased public awareness, cerebral stroke remains a leading cause of death and long-term disability worldwide. With over 600,000 new cases annually, innovative therapeutic strategies are being explored to enhance recovery outcomes. One promising approach is the use of human stem cell-derived extracellular vesicles (EVs), particularly exosomes, which function as mediators of intercellular communication. EVs have emerged as pivotal mediators of intercellular communication with immense potential in therapeutic applications. This review discusses the pioneering journey of EVs from their biogenesis and molecular cargo loading to their translation into clinical strategies for cerebral ischemic stroke therapy. While direct stem cell transplantation has faced limitations such as immune rejection, tumorigenicity, and short shelf life, human stem cell-derived EVs offer a cell-free alternative with enhanced safety, stability, and functional versatility. Preclinical studies reveal their capacity to modulate inflammation, protect neural tissue, and promote recovery through the transfer of bioactive molecules. Additionally, EVs isolated from biofluids such as blood and cerebrospinal fluid serve as promising biomarkers for stroke severity and prognosis. Despite this promise, several challenges persist—from standardizing isolation techniques and optimizing therapeutic cargo to scaling up production for clinical-grade use. This review critically examines the current understanding of EV biology, highlights the advances in stroke-related applications, and outlines key hurdles that must be addressed to unlock their full therapeutic potential.