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Cardiac repair using regenerating neonatal heart tissue-derived extracellular vesicles

Author

Listed:
  • Hanjing Li

    (Harbin Medical University
    Harbin Medical University)

  • Yining Liu

    (Harbin Medical University)

  • Yuqing Lin

    (Harbin Medical University
    Harbin Medical University)

  • Sijia Li

    (Harbin Medical University
    Harbin Medical University)

  • Chenlu Liu

    (Harbin Institute of Technology)

  • Ao Cai

    (Harbin Medical University
    Harbin Medical University)

  • Wei Li

    (Harbin Medical University
    Harbin Medical University)

  • Wanyu Zhang

    (Harbin Medical University
    Harbin Medical University)

  • Xinlu Gao

    (Harbin Medical University)

  • Zhongyu Ren

    (Harbin Medical University
    Harbin Medical University)

  • Haoyu Ji

    (Harbin Medical University)

  • Yang Yu

    (Harbin Medical University)

  • Xiuxiu Wang

    (Harbin Medical University)

  • Wenya Ma

    (Harbin Medical University)

  • Ning Wang

    (Harbin Medical University)

  • Dan Zhao

    (Harbin Medical University)

  • Tianlong Li

    (Harbin Institute of Technology)

  • Yu Liu

    (Harbin Medical University)

  • Benzhi Cai

    (Harbin Medical University
    Harbin Medical University
    Harbin Medical University)

Abstract

Neonatal mammalian hearts are capable of regenerating by inducing cardiomyocyte proliferation after injury. However, this regenerative capability in adult mammalian hearts almost disappears. Extracellular vesicles (EVs) have been shown to play vital cardioprotective roles in heart repair. Here, we report that EVs from regenerating neonatal heart tissues, after apical resection surgery (AR-Neo-EVs), exhibit stronger pro-proliferative, anti-apoptotic, and pro-angiogenesis activities than EVs from neonatal mouse cardiac tissues (Neo-EVs), effects which are absent in adult mouse heart-derived EVs (Adu-EVs). Proteomic analysis reveals the expression of Wdr75 protein, a regulator of p53, is higher in AR-Neo-EVs than in Neo-EVs. It is shown the regenerative potential of AR-Neo-EVs is abrogated when Wdr75 is knocked down. We further show that delivery of AR-Neo-EVs by sodium alginate hydrogel microspheres is an effective treatment in myocardial infraction. This work shows the potential of using EVs from regenerating tissue to trigger protective and regenerative mechanisms.

Suggested Citation

  • Hanjing Li & Yining Liu & Yuqing Lin & Sijia Li & Chenlu Liu & Ao Cai & Wei Li & Wanyu Zhang & Xinlu Gao & Zhongyu Ren & Haoyu Ji & Yang Yu & Xiuxiu Wang & Wenya Ma & Ning Wang & Dan Zhao & Tianlong L, 2025. "Cardiac repair using regenerating neonatal heart tissue-derived extracellular vesicles," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56384-x
    DOI: 10.1038/s41467-025-56384-x
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    References listed on IDEAS

    as
    1. Bin Yu & Hekai Li & Zhaowenbin Zhang & Peier Chen & Ling Wang & Xianglin Fan & Xiaodong Ning & Yuxuan Pan & Feiran Zhou & Xinyi Hu & Jiang Chang & Caiwen Ou, 2023. "Extracellular vesicles engineering by silicates-activated endothelial progenitor cells for myocardial infarction treatment in male mice," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Masanori Sano & Tohru Minamino & Haruhiro Toko & Hideyuki Miyauchi & Masayuki Orimo & Yingjie Qin & Hiroshi Akazawa & Kaoru Tateno & Yosuke Kayama & Mutsuo Harada & Ippei Shimizu & Takayuki Asahara & , 2007. "p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload," Nature, Nature, vol. 446(7134), pages 444-448, March.
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