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

  • Nat Commun. 2023 Nov 13;14(1):7334. doi: 10.1038/s41467-023-43153-x.
Ling Guo  #  1  2 ,  Qiang Yang  #  3 ,  Runxiu Wei  3 ,  Wenjun Zhang  3 ,  Na Yin  3 ,  Yuling Chen  3 ,  Chao Xu  4 ,  Changrui Li  5 ,  Randy P Carney  6 ,  Yuanpei Li  7 ,  Min Feng  8
Affiliations
  • 1. School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou, 510006, P.R. China. [email protected].
  • 2. Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, P. R. China. [email protected].
  • 3. School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou, 510006, P.R. China.
  • 4. Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, P. R. China.
  • 5. Guangzhou Zhixin High School, Zhixin South Road, Guangzhou, 510080, P.R. China.
  • 6. Department of Biomedical Engineering, University of California Davis, Davis, CA, 95616, USA. [email protected].
  • 7. Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, 95616, USA. [email protected].
  • 8. School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou, 510006, P.R. China. [email protected].
  • # Contributed equally.
PMID: 37957174 DOI: 10.1038/s41467-023-43153-x
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.

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