周细胞
血运重建
伊诺斯
细胞生物学
医学
再生(生物学)
再灌注损伤
内皮干细胞
一氧化氮
缺血
心脏病学
化学
内科学
生物
一氧化氮合酶
生物化学
心肌梗塞
体外
作者
Ling Guo,Qiang Yang,Runxiu Wei,Wenjun Zhang,Na Yin,Yuling Chen,Chao Xu,Changrui Li,Randy P. Carney,Yuanpei Li,Min Feng
标识
DOI:10.1038/s41467-023-43153-x
摘要
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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