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Enhanced pericyte-endothelial interactions through NO-boosted extracellular vesicles drive revascularization in a mouse model of ischemic injury

Author

Listed:
  • Ling Guo

    (Sun Yat-sen University, University Town
    Hainan University)

  • Qiang Yang

    (Sun Yat-sen University, University Town)

  • Runxiu Wei

    (Sun Yat-sen University, University Town)

  • Wenjun Zhang

    (Sun Yat-sen University, University Town)

  • Na Yin

    (Sun Yat-sen University, University Town)

  • Yuling Chen

    (Sun Yat-sen University, University Town)

  • Chao Xu

    (Hainan University)

  • Changrui Li

    (Guangzhou Zhixin High School)

  • Randy P. Carney

    (University of California Davis)

  • Yuanpei Li

    (University of California Davis)

  • Min Feng

    (Sun Yat-sen University, University Town)

Abstract

Despite improvements in medical and surgical therapies, a significant portion of patients with critical limb ischemia (CLI) are considered as “no option” for revascularization. In this work, a nitric oxide (NO)-boosted and activated nanovesicle regeneration kit (n-BANK) is constructed by decorating stem cell-derived nanoscale extracellular vesicles with NO nanocages. Our results demonstrate that n-BANKs could store NO in endothelial cells for subsequent release upon pericyte recruitment for CLI revascularization. Notably, n-BANKs enable endothelial cells to trigger eNOS activation and form tube-like structures. Subsequently, eNOS-derived NO robustly recruits pericytes to invest nascent endothelial cell tubes, giving rise to mature blood vessels. Consequently, n-BANKs confer complete revascularization in female mice following CLI, and thereby achieve limb preservation and restore the motor function. In light of n-BANK evoking pericyte-endothelial interactions to create functional vascular networks, it features promising therapeutic potential in revascularization to reduce CLI-related amputations, which potentially impact regeneration medicine.

Suggested Citation

  • Ling Guo & Qiang Yang & Runxiu Wei & Wenjun Zhang & Na Yin & Yuling Chen & Chao Xu & Changrui Li & Randy P. Carney & Yuanpei Li & Min Feng, 2023. "Enhanced pericyte-endothelial interactions through NO-boosted extracellular vesicles drive revascularization in a mouse model of ischemic injury," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43153-x
    DOI: 10.1038/s41467-023-43153-x
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    References listed on IDEAS

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    1. David Holmes, 2017. "Critical limb ischaemia: artery repair," Nature, Nature, vol. 548(7668), pages 41-41, August.
    2. David Holmes, 2017. "Saving life and limb," Nature, Nature, vol. 548(7668), pages 42-43, August.
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