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施万细胞和牙髓间质干细胞对脊髓损伤实验模型中 AIM2 炎性小体活性的比较影响。

The Comparative Effects of Schwann Cells and Wharton's Jelly Mesenchymal Stem Cells on the AIM2 Inflammasome Activity in an Experimental Model of Spinal Cord Injury.

机构信息

Department of Anatomy, Faculty of Medicine, Abadan University of Medical Sciences, Abadan, Iran.

Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Digital Health, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Neuroscience. 2023 Dec 15;535:1-12. doi: 10.1016/j.neuroscience.2023.10.011. Epub 2023 Oct 27.

Abstract

Inflammasome activation and the consequent release of pro-inflammatory cytokines play a crucial role in the development of sensory/motor deficits following spinal cord injury (SCI). Immunomodulatory activities are exhibited by Schwann cells (SCs) and Wharton's jelly mesenchymal stem cells (WJ-MSCs). In this study, we aimed to compare the effectiveness of these two cell sources in modulating the absent in melanoma 2 (AIM2) inflammasome complex in rats with SCI. The Basso, Beattie, Bresnahan (BBB) test, Nissl staining, and Luxol fast blue (LFB) staining were performed to evaluate locomotor function, neuronal survival, and myelination, respectively. Real-time polymerase chain reaction (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA) were employed to analyze the gene and protein expressions of inflammasome components, including AIM2, ASC, caspase-1, interleukin-1β (IL-1β), and IL-18. Both gene and protein expressions of all evaluated factors were decreased after SC or WJ-MSC treatment, with a more pronounced effect observed in the SCs group (P < 0.05). Additionally, SCs promoted neuronal survival and myelination. Moreover, the administration of 3 × 10 cells resulted in motor recovery improvement in both treatment groups (P < 0.05). Although not statistically significant, these effects were more prominent in the SC-treated animals. In conclusion, SC therapy demonstrated greater efficacy in targeting AIM2 inflammasome activation and the associated inflammatory pathway in SCI experiments compared to WJ-MSCs.

摘要

炎性小体的激活以及随之而来的促炎细胞因子的释放,在脊髓损伤(SCI)后感觉/运动功能障碍的发展中起着至关重要的作用。施万细胞(SCs)和牙髓间质干细胞(WJ-MSCs)表现出免疫调节活性。在这项研究中,我们旨在比较这两种细胞来源在调节 SCI 大鼠缺失黑色素瘤 2(AIM2)炎性小体复合物方面的有效性。采用 Basso、Beattie、Bresnahan(BBB)测试、尼氏染色和卢索快速蓝(LFB)染色分别评估运动功能、神经元存活和髓鞘形成。实时聚合酶链反应(RT-PCR)、Western blot 和酶联免疫吸附测定(ELISA)用于分析炎性小体成分(包括 AIM2、ASC、半胱天冬酶-1、白细胞介素-1β(IL-1β)和白细胞介素-18)的基因和蛋白表达。SC 或 WJ-MSC 处理后,所有评估因子的基因和蛋白表达均降低,SCs 组的效果更为明显(P<0.05)。此外,SCs 促进神经元存活和髓鞘形成。此外,在两个治疗组中,给予 3×10 个细胞均可改善运动功能恢复(P<0.05)。虽然没有统计学意义,但在接受 SC 治疗的动物中,这些效果更为明显。总之,与 WJ-MSCs 相比,SCs 治疗在 SCI 实验中靶向 AIM2 炎性小体激活及其相关炎症途径的效果更为显著。

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