Harnessing extracellular vesicles for ischemic stroke management

Abstract Extracellular vesicles (EVs) are versatile, cell-derived complexes that serve as complete package of biologically important molecules, released during both normal and pathological processes. With rapid advancements in EVs research, there has been a shift in its therapeutic applications, clinical development, and commercialization. EVs have been extensively studied for their potential to mitigate ischemic stroke pathological mechanisms, such as excitotoxicity, immune response, blood-brain barrier (BBB) dysfunction, neuroinflammation, and apoptosis. EVs innate ability to protect molecular cargo (proteins, DNA or RNA) from enzymatic degradation, their natural ability to transverse BBB, high cargo-loading efficiency and superior biocompatibility make them ideal candidates for targeted drug delivery systems in ischemic stroke. Their presence in most biofluids and changes in their contents during disease conditions, support investigation of EVs as promising minimally invasive biomarkers for the early diagnosis and treatment monitoring of ischemic stroke. Moreover, EVs in combination with other therapeutic agents have considerable potential for clinical translation. This perspective provides a comprehensive overview of current literature on EV-based systems in stroke management, highlighting their role as standalone therapeutics, presenting opportunities for cargo delivery, biomarkers discovery, and synergistic component of combination therapies. Additionally, the ongoing clinical trials are discussed along with the challenges and considerations required to advance the clinical translation and adaptation of EV-based systems for ischemic stroke management.