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Progress on the physiological functions and clinical applications of red blood cellderived extracellular vesicles

PAN Hong-Yu¹, CHENG Si-Yu², WANG Jing-Wei¹, LIN Le-Xuan¹, LI Xin-Yu¹, GAO Cheng-Jie¹, SHI Li-Hong^1,3,*

¹State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China；²Tianjin Medical University, Haihe Laboratory of Cell Ecosystem, Tianjin 300070, China；³Tianjin Institutes of Health Science, Tianjin 301600, China

Abstract

Red blood cell-derived extracellular vesicles (RBC-EVs) are one of the most abundant types of extracellular vesicles (EVs) in the blood, playing a crucial role in intercellular communication, disease progression, and medical applications. The structure of RBC-EVs differs from that of red blood cells (RBCs), characterized by phosphatidylserine externalization, reduced membrane proteins, and encapsulation of bioactive molecules such as hemoglobin and miRNAs. RBC-EVs primarily exist as microvesicles and exosomes, which are generated through membrane budding and the multivesicular bodies pathway, respectively. Their clearance in vivo mainly relies on phagocytosis by hepatic Kupffer cells. Physiologically, RBC-EVs maintain the normal physiological functions of RBCs by removing damaged and senescent signals from the RBC membrane, regulate organismal homeostasis through participation in nitric oxide balance and anticoagulant processes, and also engage in immune regulation and exert certain antiviral effects. Additionally, they serve as intercellular information carriers to function in various diseases. Endowed with advantages such as high biocompatibility and low immunogenicity, RBC-EVs have demonstrated enormous clinical application potential as carriers for small-molecule drugs (e.g., nucleic acids) in fields including hematological diseases, liver diseases, and cancer. This review systematically summarizes the composition and structure, biogenesis and clearance mechanisms, main physiological functions, clinical applications, and future prospects of RBC-EVs.

Key words: red blood cell; extracellular vesicles; procoagulation and anticoagulation; immunomodulation; microcarrier

Received: 　　Accepted:

Corresponding author: 石莉红　　E-mail:

DOI: 10.13294/j.aps.2026.0068

Citing This Article：

PAN Hong-Yu, CHENG Si-Yu, WANG Jing-Wei, LIN Le-Xuan, LI Xin-Yu, GAO Cheng-Jie, SHI Li-Hong. Progress on the physiological functions and clinical applications of red blood cellderived extracellular vesicles. Acta Physiol Sin 2026; 78 (4): 789-802 (in Chinese with English abstract).