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生物工程外泌体治疗器官缺血再灌注损伤。

Bioengineering exosomes for treatment of organ ischemia-reperfusion injury.

机构信息

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.

Department of Pharmaceutical Nanotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Life Sci. 2022 Aug 1;302:120654. doi: 10.1016/j.lfs.2022.120654. Epub 2022 May 18.

DOI:10.1016/j.lfs.2022.120654
PMID:35597547
Abstract

Ischemia-reperfusion (I/R) injury is a leading cause of death worldwide. It arises from blood reflowing after tissue hypoxia induced by ischemia that causes severe damages due to the accumulation of reactive oxygen species and the activation of inflammatory responses. Exosomes are the smallest members of the extracellular vesicles' family, which originate from nearly all eukaryotic cells. Exosomes have a great potential in the treatment of I/R injury either in native or modified forms. Native exosomes are secreted by different cell types, such as stem cells, and contain components such as specific miRNA molecules with tissue protective properties. On the other hand, exosome bioengineering has recently received increased attention in context of current advances in the purification, manipulation, biological characterization, and pharmacological applications. There are various pre-isolation and post-isolation manipulation approaches that can be utilized to increase the circulation half-life of exosomes or the availability of their bioactive cargos in the target site. In this review, the various therapeutic actions of native exosomes in different I/R injury will be discussed first. Exosome bioengineering approaches will then be explained, including pre- and post-isolation manipulation methods, applicability for delivery of bioactive agents to injured tissue, clinical translation issues, and future perspectives.

摘要

缺血再灌注(I/R)损伤是全球范围内导致死亡的主要原因。它是由组织缺氧引起的血液再灌注引起的,由于活性氧物质的积累和炎症反应的激活,会导致严重的损伤。外泌体是细胞外囊泡家族中最小的成员,几乎起源于所有真核细胞。外泌体具有很大的潜力,可以通过天然或修饰的形式来治疗 I/R 损伤。天然外泌体由不同的细胞类型(如干细胞)分泌,其中包含具有组织保护特性的特定 miRNA 分子等成分。另一方面,外泌体生物工程最近受到了越来越多的关注,因为在纯化、操作、生物学特性和药理学应用方面取得了新的进展。有各种预分离和后分离操作方法可用于增加外泌体的循环半衰期或目标部位其生物活性有效成分的可用性。在这篇综述中,首先将讨论天然外泌体在不同的 I/R 损伤中的各种治疗作用。然后将解释外泌体生物工程方法,包括预分离和后分离操作方法、将生物活性物质递送至损伤组织的适用性、临床转化问题和未来展望。

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1
Bioengineering exosomes for treatment of organ ischemia-reperfusion injury.生物工程外泌体治疗器官缺血再灌注损伤。
Life Sci. 2022 Aug 1;302:120654. doi: 10.1016/j.lfs.2022.120654. Epub 2022 May 18.
2
Exosomes-carried microRNA-26b-5p regulates microglia M1 polarization after cerebral ischemia/reperfusion.外泌体携带的 microRNA-26b-5p 调节脑缺血/再灌注后小胶质细胞 M1 极化。
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Stem Cell-Based Acellular Therapy: Insight into Biogenesis, Bioengineering and Therapeutic Applications of Exosomes.基于干细胞的去细胞治疗:外泌体的发生、生物工程和治疗应用的深入了解。
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Human urine-derived stem cells protect against renal ischemia/reperfusion injury in a rat model via exosomal which targets .人尿源干细胞通过外泌体靶向 保护大鼠肾缺血/再灌注损伤。
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Profiles of lipid, protein and microRNA expression in exosomes derived from intestinal epithelial cells after ischemia-reperfusion injury in a cellular hypoxia model.细胞缺氧模型中肠上皮细胞缺血再灌注损伤后衍生的外泌体中的脂质、蛋白质和 microRNA 表达谱。
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Neuronal Exosomes Secreted under Oxygen-Glucose Deprivation/Reperfusion Presenting Differentially Expressed miRNAs and Affecting Neuronal Survival and Neurite Outgrowth.在氧糖剥夺/再灌注条件下分泌的神经元外泌体呈现出差异表达的微小RNA,并影响神经元存活和轴突生长。
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BMSCs protect against renal ischemia-reperfusion injury by secreting exosomes loaded with miR-199a-5p that target BIP to inhibit endoplasmic reticulum stress at the very early reperfusion stages.BMSCs 通过分泌含有 miR-199a-5p 的外泌体来保护肾脏免受缺血再灌注损伤,miR-199a-5p 靶向 BIP 以抑制内质网应激在再灌注早期阶段。
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Tubular cell-derived exosomal miR-150-5p contributes to renal fibrosis following unilateral ischemia-reperfusion injury by activating fibroblast and .管状细胞来源的外泌体 miR-150-5p 通过激活成纤维细胞和 ,导致单侧缺血再灌注损伤后的肾脏纤维化。
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Exosomes derived from PEDF modified adipose-derived mesenchymal stem cells ameliorate cerebral ischemia-reperfusion injury by regulation of autophagy and apoptosis.脂肪来源间充质干细胞来源的外泌体通过调控自噬和凋亡改善脑缺血再灌注损伤。
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Exosomes derived from human adipose-derived stem cells alleviate hepatic ischemia-reperfusion (I/R) injury through the miR-183/ALOX5 axis.人脂肪间充质干细胞来源的外泌体通过 miR-183/ALOX5 轴减轻肝缺血再灌注(I/R)损伤。
FASEB J. 2023 Mar;37(3):e22782. doi: 10.1096/fj.202200277R.

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