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沃顿胶衍生外泌体对HIG-82滑膜细胞炎症介质产生的影响

The Impact of Wharton's Jelly-derived Exosomes on the Production of Inflammatory Mediators from HIG-82 Synoviocytes.

作者信息

Fotouhi Ali, Hosseini Maryam, Aghebati-Maleki Ali, Soltani-Zangbar Mohammad Sadegh, Parsania Sara, Mardi Amirhossein, Aghebati-Maleki Leili

机构信息

Department of Orthopedic Surgery, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Iran J Immunol. 2024 Sep 22;21(3):243-254. doi: 10.22034/iji.2024.101823.2760.

DOI:10.22034/iji.2024.101823.2760
PMID:39306730
Abstract

BACKGROUND

Osteoarthritis (OA) is the most common joint disease worldwide. Routine treatment options are limited, and total knee replacement surgeries often come with complications. In recent years, the use of biologics, such as Wharton's jelly (Wj) derived from the umbilical cord (UC), has gained popularity. While mesenchymal stem cells (MSCs) derived from Wj show promise in restoring articular cartilage, they also have some limitations. Recent studies have indicated that exosomes isolated from acellular Wj may offer advantages under certain conditions.

OBJECTIVE

To investigate the anti-inflammatory properties of exosomes isolated from Wj in synoviocytes.

METHODS

Decellularization of Wj was performed using sterile umbilical cords obtained from patients. Next, the exosomes were isolated from Wj using ultracentrifugation. After characterizing the exosomes, they were co-cultured with inflammatory synovial fibroblast cells (HIG-82) for 24 hours. Then, the gene expression levels and protein contents of some important inflammatory mediators including metalloproteinase-13 (MMP-13), cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS) were measured in the cells using real-time PCR and ELISA tests, respectively.

RESULTS

The expression levels of MMP-13, COX-2, and iNOS genes were significantly reduced in the cultured cells treated with exosomes compared to untreated cells. Moreover, the content of MMP-13, COX-2, and iNOS proteins were significantly lower in the supernatant of the cultured cells compared to the control.

CONCLUSION

Wj-derived exosomes exhibit notable anti-inflammatory properties, which can help mitigate inflammation in the synovial environment of joints. However, further research is required to fully understand their benefits and potential applications in treating osteoarthritis.

摘要

背景

骨关节炎(OA)是全球最常见的关节疾病。常规治疗选择有限,全膝关节置换手术常伴有并发症。近年来,源自脐带(UC)的华通氏胶(Wj)等生物制剂的使用日益普遍。虽然源自Wj的间充质干细胞(MSCs)在恢复关节软骨方面显示出前景,但它们也有一些局限性。最近的研究表明,从无细胞Wj中分离出的外泌体在某些条件下可能具有优势。

目的

研究从Wj中分离出的外泌体在滑膜细胞中的抗炎特性。

方法

使用从患者获得的无菌脐带对Wj进行去细胞处理。接下来,通过超速离心从Wj中分离出外泌体。对外泌体进行表征后,将它们与炎性滑膜成纤维细胞(HIG-82)共培养24小时。然后,分别使用实时PCR和ELISA检测在细胞中测量包括金属蛋白酶-13(MMP-13)、环氧化酶-2(COX2)和诱导型一氧化氮合酶(iNOS)在内的一些重要炎症介质的基因表达水平和蛋白质含量。

结果

与未处理的细胞相比,用外泌体处理的培养细胞中MMP-13、COX-2和iNOS基因的表达水平显著降低。此外,与对照相比,培养细胞上清液中MMP-13、COX-2和iNOS蛋白的含量显著降低。

结论

源自Wj的外泌体具有显著的抗炎特性,这有助于减轻关节滑膜环境中的炎症。然而,需要进一步研究以充分了解它们在治疗骨关节炎中的益处和潜在应用。

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