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脂肪间充质干细胞分泌细胞外囊泡:一种用于犬肾缺血再灌注损伤的潜在无细胞治疗方法。

Adipose-derived mesenchymal stem cells secrete extracellular vesicles: A potential cell-free therapy for canine renal ischaemia-reperfusion injury.

机构信息

Department of Veterinary Surgery, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

Chongqing Fengdu Agricultural Science and Technology Development Group Co. Ltd, Chongqing, China.

出版信息

Vet Med Sci. 2023 May;9(3):1134-1142. doi: 10.1002/vms3.1105. Epub 2023 Mar 13.

Abstract

BACKGROUND

Adipose-derived mesenchymal stem cells (ADMSCs) and their extracellular vesicles (EVs) are a promising source of therapies for ischaemia-reperfusion (IR) because of their potent anti-inflammatory and immunomodulatory properties.

OBJECTIVES

The aims of this study were to explore the therapeutic efficacy and potential mechanism of ADMSC-EVs in canine renal IR injury.

METHODS

Mesenchymal stem cells (MSCs) and EVs were isolated and characterised for surface markers. A canine IR model administered with ADMSC-EVs was used to evaluate therapeutic effects on inflammation, oxidative stress, mitochondrial damage and apoptosis.

RESULTS

CD105, CD90 and beta integrin ITGB were positively expressed in MSCs, while CD63, CD9 and intramembrane marker TSG101 were positively expressed in EVs. Compared with the IR model group, there was less mitochondrial damage and reduction in quantity of mitochondria in the EV treatment group. Renal IR injury led to severe histopathological lesions and significant increases in biomarkers of renal function, inflammation and apoptosis, which were attenuated by the administration of ADMSC-EVs.

CONCLUSIONS

Secretion of EVs by ADMSCs exhibited therapeutic potential in renal IR injury and may lead to a cell-free therapy for canine renal IR injury. These findings revealed that canine ADMSC-EVs potently attenuate renal IR injury-induced renal dysfunction, inflammation and apoptosis, possibly by reducing mitochondrial damage.

摘要

背景

脂肪间充质干细胞(ADMSCs)及其细胞外囊泡(EVs)因其强大的抗炎和免疫调节特性,成为治疗缺血再灌注(IR)的有前途的治疗方法。

目的

本研究旨在探讨 ADMSC-EVs 在犬肾 IR 损伤中的治疗效果及潜在机制。

方法

分离和鉴定间充质干细胞(MSCs)和 EVs 的表面标志物。使用 ADMSC-EVs 处理的犬 IR 模型来评估对炎症、氧化应激、线粒体损伤和细胞凋亡的治疗效果。

结果

MSCs 中 CD105、CD90 和β整合素 ITGB 呈阳性表达,而 EVs 中 CD63、CD9 和膜内标记物 TSG101 呈阳性表达。与 IR 模型组相比,EV 治疗组的线粒体损伤较少,线粒体数量减少。肾 IR 损伤导致严重的组织病理学损伤,肾功能、炎症和细胞凋亡的生物标志物显著增加,而 ADMSC-EVs 的给予则减轻了这些变化。

结论

ADMSCs 的 EV 分泌在肾 IR 损伤中表现出治疗潜力,并可能导致犬肾 IR 损伤的无细胞治疗。这些发现表明,犬 ADMSC-EVs 可有效减轻肾 IR 损伤引起的肾功能障碍、炎症和细胞凋亡,可能是通过减少线粒体损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bb1/10188084/618b28a09673/VMS3-9-1134-g003.jpg

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