2. Academic Validation
  3. Extracellular vesicles derived from menstrual blood-derived mesenchymal stem cells suppress inflammatory atherosclerosis by inhibiting NF-κB signaling

Extracellular vesicles derived from menstrual blood-derived mesenchymal stem cells suppress inflammatory atherosclerosis by inhibiting NF-κB signaling

  • BMC Med. 2025 Oct 15;23(1):565. doi: 10.1186/s12916-025-04390-7.
Jinjin Yu # 1 2 3,  Xiaotian Liu # 4,  Lele Jin # 5,  Han Li # 6,  Suhui Wang 1,  Yongwei Yang 7,  Xilian Chen 7,  Hongxia Wang 8,  Yingke Li 9,  Jie Lian 9,  Chao Shi 10,  Haihui Li 10,  Yong Zhang 5,  Emmanuel Jairaj Moses 11,  Hongxing Zhang 12,  Chunfu Zheng 13,  Xinxing Zhu 14
Affiliations

Affiliations

  • 1 Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, First Affiliated Hospital, Bengbu Medical University, Bengbu, 233004, China.
  • 2 Regenerative Medicine Sciences Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, 13200, Malaysia.
  • 3 School of Psychology, Xinxiang Medical University, Xinxiang, 453003, China.
  • 4 Research Center of Clinical Laboratory Science, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233004, China.
  • 5 Department of Respiratory and Critical Care Medicine, First Affiliated Hospital, Bengbu Medical University, 287 Changhuai Road, Bengbu, Anhui Province, 233004, China.
  • 6 National Joint Engineering Laboratory of Stem Cells and Biotherapy, School of Life Science and Technology, Stem Cells and Biotherapy Engineering Research Center of Henan, Xinxiang Medical University, Xinxiang, 453003, China.
  • 7 Yantai Qishan Hospital, Yantai, 264001, China.
  • 8 Cao County Infectious Disease Hospital, Heze, 274000, China.
  • 9 Henan Joint International Research Laboratory of Stem Cell Medicine, College of Biomedical Engineering, Xinxiang Medical University, Xinxiang, 453003, China.
  • 10 Department of Cardiac Surgery, First Affiliated Hospital, Bengbu Medical University, Bengbu, 233004, China.
  • 11 Regenerative Medicine Sciences Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, 13200, Malaysia. emmanuel_jm@usm.my.
  • 12 School of Psychology, Xinxiang Medical University, Xinxiang, 453003, China. zhanghxzhang@hotmail.com.
  • 13 Department of Microbiology, Immunology & Infection Diseases, Health Research Innovation Centre, University of Calgary, 3330 Hospital Drive NW, CalgaryAlberta, AB, T2N 4N1, Canada. zheng.alan@hotmail.com.
  • 14 Department of Respiratory and Critical Care Medicine, First Affiliated Hospital, Bengbu Medical University, 287 Changhuai Road, Bengbu, Anhui Province, 233004, China. 012023112@bbmc.edu.cn.
  • # Contributed equally.
PMID: 41094553 DOI: 10.1186/s12916-025-04390-7
Abstract

Background: Numerous studies have highlighted the beneficial effects of mesenchymal stem cells (MSCs) in various inflammatory disorders. However, the regulatory role of MSCs in inflammatory atherosclerosis and the molecular mechanisms underlying their anti-inflammatory properties have largely remained elusive.

Methods: Differential ultracentrifugation was performed to isolate extracellular vesicles (EVs) released by menstrual blood-derived mesenchymal stem cells (MenSCs). An apoE knockout atherosclerotic animal model was employed to investigate the regulatory effect of MenSC-EVs on inflammatory atherosclerosis. miRNA microarray screening analyses were conducted to identify potential effectors in MenSC-EVs that play a key role in the suppression of atherosclerosis mediated by the EVs.

Results: We demonstrated the remarkable potential of MenSC-EVs in alleviating atherosclerosis through the NF-κB signaling pathway. miR-574-5p serves as a crucial effector molecule transported by MenSC-EVs, suppressing endothelial inflammation and promoting nitric oxide production. This regulation contributes to the attenuation of atherosclerosis by regulating the abundance of c-Rel. The miR-574-5p/c-Rel axis shows significant clinical relevance to atherosclerosis.

Conclusions: This study reveals that the engineering of EVs derived from MenSCs holds significant promise as a strategic clinical approach for addressing inflammatory atherosclerosis.

Keywords

Extracellular vesicles; Inflammatory atherosclerosis; MenSCs; MiR-574-5p; NF-κB signaling.

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