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

Ling Guo (), Qiang Yang, Runxiu Wei, Wenjun Zhang, Na Yin, Yuling Chen, Chao Xu, Changrui Li, Randy P. Carney (), Yuanpei Li () and Min Feng ()
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Ling Guo: Sun Yat-sen University, University Town
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

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43153-x

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