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

  • J Extracell Vesicles. 2025 Jan;14(1):e70041. doi: 10.1002/jev2.70041.
Libin Hu  1  2  3 ,  Zihang Chen  1  2  3 ,  Jianglong Lu  4 ,  Shandong Jiang  1  2 ,  Haopu Lin  1  2 ,  Jiayin Zhou  1  2 ,  Ning Wang  4 ,  Chao Ding  4 ,  Weifang Ni  4 ,  Haitao Peng  4 ,  Yin Li  1  2 ,  Xuchao He  1  2 ,  Jianru Li  1  2 ,  Chaohui Jing  5 ,  Yang Cao  6 ,  Hang Zhou  1  2  3 ,  Feng Yan  1  2  3 ,  Gao Chen  1  2  3
Affiliations
  • 1. Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  • 2. Zhejiang Key Laboratory of Research and Transformation for Major Neurosurgical Diseases, Hangzhou, China.
  • 3. State Key Laboratory of Transvascular Implantation Devices, Hangzhou, China.
  • 4. Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 5. Department of Neurosurgery, XinHua Hospital affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, China.
  • 6. Department of Neurosurgery, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China.
PMID: 39868438 DOI: 10.1002/jev2.70041
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.

Keywords
ARG1; BMDM; EVs; ICH; microglia; phagocytosis.
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