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

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

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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