Apoptotic vesicles derived from bone marrow mesenchymal stem cells increase angiogenesis in a hind limb ischemia model via the NAMPT/SIRT1/FOXO1 axis

作者：Jinxing Chen, Zekun Shen, Bingyi Chen, Shuang Liu, Yifan Mei, Kai Li, Zi-Yang Peng, Chaoshuai Feng, Weiyi Wang, Shaoying Lu · 发表于：Stem Cell Research & Therapy · 年份：2025 · DOI：10.1186/s13287-025-04245-1 · 被引用次数：6 · 研究领域：Extracellular vesicles in disease、FOXO transcription factor regulation、Circular RNAs in diseases

BACKGROUND: Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral arterial disease (PAD). Mesenchymal stem cell (MSC) transplantation holds promise as a treatment for CLTI; however, the harsh local environment poses challenges to its effectiveness. Apoptotic vesicles (ApoVs) are extracellular vesicles produced by cells undergoing apoptosis, and they can carry various biomolecules from their parent cells, including proteins, RNA, DNA, lipids, ions, and gas neurotransmitters. ApoVs play significant roles in anti-inflammatory responses, anti-tumor activities, and tissue regeneration through intercellular communication, and they have demonstrated potential as drug carriers. In this study, we investigated the potential of bone marrow stem cell (BMSC)-derived ApoVs for treating CLTI. METHODS: In vivo, we explored the therapeutic effect of ApoVs on a hindlimb ischemia model through Laser Doppler, matrigel plug assay, and histological analysis. In vitro, we analyzed the effects of ApoVs on the proliferation, migration, and angiogenesis of HUVECs and explored the uptake process of ApoVs. In addition, Proteomic analysis, western blotting, quantitative real-time PCR, shRNA, and siRNA were used to analyze ApoVs-induced HUVECs activation and downstream signaling pathways. RESULTS: BMSCs transplantation showed improvement in a hind limb ischemia model, and this effect still exists after apoptosis of BMSCs. Subsequently, ApoVs of BMSCs were isolated and found to imp...