Extracellular Vesicles From Bone Marrow‐Derived Macrophages Enriched in ARG1 Enhance Microglial Phagocytosis and Haematoma Clearance Following Intracerebral Haemorrhage

ABSTRACT Microglial phagocytosis of haematomas is crucial for neural functional recovery following intracerebral haemorrhage (ICH), a process regulated by various factors from within and outside the central nervous system (CNS). Extracellular vesicles (EVs), significant mediators of intercellular communication, have been demonstrated to play a pivotal role in the pathogenesis and progression of CNS diseases. However, the regulatory role of endogenous EVs on the phagocytic capacity of microglia post‐ICH remains elusive. Utilising multi‐omics analysis of brain tissue‐derived EVs proteomics and single‐cell RNA sequencing, this study identified that bone marrow‐derived macrophages (BMDMs) potentially enhance microglial phagocytosis via EVs following ICH. By blocking BMDMs and reducing ARG1 in BMDM‐derived EVs, we demonstrated that BMDMs facilitate erythrophagocytosis by delivering ARG1 to microglia via EVs post‐ICH. EVs‐carried ARG1 was found to augment phagocytosis by promoting RAC1‐dependent cytoskeletal remodelling in microglia. Collectively, this research uncovers an intercellular communication pathway from BMDMs to microglia mediated by EVs post‐ICH. This provides a novel paradigm for EV‐mediated intercellular communication mechanisms and suggests a promising therapeutic potential for BMDM‐derived EVs in the treatment of ICH.