Taghavi Samin, Keshtkar Somayeh, Abedanzadeh Mozhgan, Hashemi Mehrdad, Heidari Reza, Abolmaali Samira Sadat, Dara Mahintaj, Aghdaei Mahdokht Hossein, Sabegh Alireza, Azarpira Negar
Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Stem Cells Int. 2025 Jan 15;2025:3106634. doi: 10.1155/sci/3106634. eCollection 2025.
Renal dysfunction due to ischemia-reperfusion injury (IRI) is a common problem after kidney transplantation. In recent years, studies on animal models have shown that exosomes derived from mesenchymal stem cells (MSC-Exo) play an important role in treating acute kidney injury (AKI) and promoting tissue repair. The microneedle patch provides a noninvasive and targeted delivery system for exosomes. The purpose of this innovative approach is to combine MSC-Exo with microneedle patches. Exosomes were isolated from MSCs, characterized, and placed in the prepared microneedle patch. Then this construct was applied to the IRI mice model. After 7 days, the gene expression of miR-34a and its targets B-cell lymphoma-2 (BCL-2) and BCL-2-associated X (BAX), along with reactive oxygen species (ROS) and lipid peroxidation (LPO) production, was investigated. Additionally, renoprotection was evaluated for measuring blood urea nitrogen (BUN) and creatinine (Cr) and histopathology detection. After using microneedle patches containing exosomes, the reduction of miR-34a and BAX and enhancement of BCL-2 were observed. Moreover, treatment by this construct decreased the production of ROS, LPO, BUN, and Cr and improved tissue damage. The use of a microneedle patch containing exosomes is a noninvasive method that enables the release of exosomes in a slow manner. In comparison to exosome injection alone, microneedle patch-exosome treatment offers a longer and more targeted effect that improves renal IRI dysfunction and reduces tissue damage, potentially facilitating the clinical application of exosomes and improving graft survival.
缺血再灌注损伤(IRI)导致的肾功能障碍是肾移植后常见的问题。近年来,对动物模型的研究表明,间充质干细胞来源的外泌体(MSC-Exo)在治疗急性肾损伤(AKI)和促进组织修复方面发挥着重要作用。微针贴片为外泌体提供了一种非侵入性的靶向递送系统。这种创新方法的目的是将MSC-Exo与微针贴片相结合。从间充质干细胞中分离出外泌体,进行表征,然后置于制备好的微针贴片中。接着将这种构建体应用于IRI小鼠模型。7天后,研究了miR-34a及其靶标B细胞淋巴瘤-2(BCL-2)和BCL-2相关X蛋白(BAX)的基因表达,以及活性氧(ROS)和脂质过氧化(LPO)的产生情况。此外,通过测量血尿素氮(BUN)和肌酐(Cr)以及组织病理学检测来评估肾脏保护作用。使用含有外泌体的微针贴片后,观察到miR-34a和BAX减少,BCL-2增加。此外,这种构建体治疗降低了ROS、LPO、BUN和Cr的产生,并改善了组织损伤。使用含有外泌体的微针贴片是一种非侵入性方法,能够以缓慢的方式释放外泌体。与单独注射外泌体相比,微针贴片-外泌体治疗具有更长时间和更具靶向性的效果,可改善肾IRI功能障碍并减少组织损伤,可能有助于外泌体的临床应用并提高移植物存活率。