2. Academic Validation
  3. Targeted immunomodulation therapy for cardiac repair by platelet membrane engineering extracellular vesicles via hitching peripheral monocytes

Targeted immunomodulation therapy for cardiac repair by platelet membrane engineering extracellular vesicles via hitching peripheral monocytes

  • Biomaterials. 2022 May;284:121529. doi: 10.1016/j.biomaterials.2022.121529.
Qiyu Li 1,  Zheyong Huang 1,  Qiaozi Wang 1,  Jinfeng Gao 1,  Jing Chen 1,  Haipeng Tan 1,  Su Li 1,  Zhengmin Wang 1,  Xueyi Weng 1,  Hongbo Yang 1,  Zhiqing Pang 2,  Yanan Song 3,  Juying Qian 4,  Junbo Ge 5
Affiliations

Affiliations

  • 1 Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Feng Lin Road, Shanghai, 200032, China; National Clinical Research Center for Interventional Medicine& Shanghai Clinical Research Center for Interventional Medicine, 180 Feng Lin Road, Shanghai, 200032, China.
  • 2 School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai, 201203, China. Electronic address: zqpang@fudan.edu.cn.
  • 3 Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Feng Lin Road, Shanghai, 200032, China; National Clinical Research Center for Interventional Medicine& Shanghai Clinical Research Center for Interventional Medicine, 180 Feng Lin Road, Shanghai, 200032, China. Electronic address: yanan.song@163.com.
  • 4 Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Feng Lin Road, Shanghai, 200032, China; National Clinical Research Center for Interventional Medicine& Shanghai Clinical Research Center for Interventional Medicine, 180 Feng Lin Road, Shanghai, 200032, China. Electronic address: Qian.juying@zs-hospital.sh.cn.
  • 5 Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Feng Lin Road, Shanghai, 200032, China; National Clinical Research Center for Interventional Medicine& Shanghai Clinical Research Center for Interventional Medicine, 180 Feng Lin Road, Shanghai, 200032, China; Institute of Biomedical Science, Fudan University, 180 Feng Lin Road, Shanghai, 200032, China.
PMID: 35447403 DOI: 10.1016/j.biomaterials.2022.121529
Abstract

Immune regulation therapies have been considered promising in the treatment of myocardial ischemia reperfusion (MI/R) injury. Mesenchymal stem cells derived extracellular vesicles (MSC-EVs) are of great potential for immune modulation by reprogramming macrophages but their therapeutic efficacy is hindered by insufficient targeting ability in vivo. Herein, we introduced the platelet membrane modified EVs (P-EVs) based on membrane fusion method to mimic the binding ability of platelets to monocytes. In the mouse model of MI/R injury, the intravenously injected P-EVs were mainly carried by circulating monocytes into the ischemic myocardium. In the inflammatory microenvironment, those monocytes subsequently differentiated into macrophages with enhanced phagocytosis, which probably promoted in-situ endocytosis of the superficial P-EVs by monocytes differentiated macrophages in large quantities. Then, the P-EVs successfully escaped from the macrophage lysosome and released the functional MicroRNAs (miRNAs) into the cytosol which facilitated the inflammatory macrophages (M1 phenotype) reprogramming to reparative macrophages (M2 phenotype). Finally, the immune microenvironment was regulated to realize cardiac repair. Thus, we supposed that the most likely delivery method was that monocytes mediated P-EVs migration into ischemic myocardium where P-EVs were mainly in-situ endocytosed by monocytes derived macrophages, which holds potential for immunoregulation on MI/R and other immune-related diseases in the future.

Keywords

Hitching; Immunomodulation; MSC-EVs; Myocardial ischemia reperfusion; Platelet membrane.

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