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生物生成的与氧相关的环境应激凋亡囊泡靶向内皮细胞。

Biogenerated Oxygen-Related Environmental Stressed Apoptotic Vesicle Targets Endothelial Cells.

机构信息

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, 200011, P. R. China.

Department of Plastic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, P. R. China.

出版信息

Adv Sci (Weinh). 2024 May;11(20):e2306555. doi: 10.1002/advs.202306555. Epub 2024 Mar 13.

DOI:10.1002/advs.202306555
PMID:38477548
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11132028/
Abstract

The dynamic balance between hypoxia and oxidative stress constitutes the oxygen-related microenvironment in injured tissues. Due to variability, oxygen homeostasis is usually not a therapeutic target for injured tissues. It is found that when administered intravenously, mesenchymal stem cells (MSCs) and in vitro induced apoptotic vesicles (ApoVs) exhibit similar apoptotic markers in the wound microenvironment where hypoxia and oxidative stress co-existed, but MSCs exhibited better effects in promoting angiogenesis and wound healing. The derivation pathway of ApoVs by inducing hypoxia or oxidative stress in MSCs to simulate oxygen homeostasis in injured tissues is improved. Two types of oxygen-related environmental stressed ApoVs are identified that directly target endothelial cells (ECs) for the accurate regulation of vascularization. Compared to normoxic and hypoxic ones, oxidatively stressed ApoVs (Oxi-ApoVs) showed the strongest tube formation capacity. Different oxygen-stressed ApoVs deliver similar miRNAs, which leads to the broad upregulation of EC phosphokinase activity. Finally, local delivery of Oxi-ApoVs-loaded hydrogel microspheres promotes wound healing. Oxi-ApoV-loaded microspheres achieve controlled ApoV release, targeting ECs by reducing the consumption of inflammatory cells and adapting to the proliferative phase of wound healing. Thus, the biogenerated apoptotic vesicles responding to oxygen-related environmental stress can target ECs to promote vascularization.

摘要

缺氧和氧化应激之间的动态平衡构成了受损组织中的氧相关微环境。由于变异性，氧平衡通常不是受损组织的治疗靶点。研究发现，静脉内给予间充质干细胞 (MSCs) 和体外诱导的凋亡小体 (ApoVs) 时，在缺氧和氧化应激共存的伤口微环境中表现出相似的凋亡标志物，但 MSCs 在促进血管生成和伤口愈合方面效果更好。通过在 MSCs 中诱导缺氧或氧化应激来模拟受损组织中的氧平衡，改善了 ApoVs 的衍生途径。鉴定出两种与氧相关的环境应激 ApoVs，它们直接针对内皮细胞 (ECs) 进行精确的血管生成调节。与常氧和低氧相比，氧化应激的 ApoVs (Oxi-ApoVs) 表现出最强的管状形成能力。不同的氧应激 ApoVs 传递相似的 miRNAs，导致 EC 磷酸激酶活性广泛上调。最后，局部递送载有 Oxi-ApoVs 的水凝胶微球促进伤口愈合。载有 Oxi-ApoV 的微球通过减少炎症细胞的消耗和适应伤口愈合的增殖期来实现 ApoV 的受控释放，靶向 ECs。因此，对氧相关环境应激做出反应的生物生成的凋亡小体可以靶向 ECs 以促进血管生成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fde/11132028/e2426e33a5e2/ADVS-11-2306555-g003.jpg
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