基于巨噬细胞M2(MP2)的细胞疗法是一种用于患有实验性自身免疫性脑脊髓炎(EAE)的动物的新型药物治疗,作为多发性硬化症(MS)的实验模型。这项系统综述和荟萃分析研究旨在评估MP2细胞疗法对EAE诱导的动物的临床评分和运动障碍的总体治疗效果。在EAE动物中进行MP2细胞治疗的所有实验均来自英语(PubMed,2022年10月2日)。Scopus,WOS,科学直接,和ISC)和波斯语(MagIran和SID)数据库。搜索策略设计使用“实验性自身免疫性脑脊髓炎,\"\"多发性硬化症,\"和\"巨噬细胞M2\"关键字。在初级和次级筛查之后,符合条件的论文是根据PRISMA2020指南选择的,使用动物研究:体内实验报告(ARRIVE)清单评估研究质量。基于随机效应模型(CMA软件,V.2).分组(EAE发作阶段,峰,和恢复)被应用,采用I2指数对异质性指数进行评估。还评估了发表偏倚和敏感性指数。P<0.05被认为是显著的,置信区间(CI)为95%。在22份收集的文件中,选择中质量到高质量的研究进行荟萃分析.手段上的差异,P值,和I2为开始,峰,和恢复阶段为0.082(CI95%:-0.323-0.159,P值:0.504,I2:67.961%),-0.606(CI95%:-1.518至-0.305,P值:0.192,I2:96.070%),和-1.103(CI95%:-1.390至-0.816,P值:0.000,I2:30.880%),分别和总体效果为-0.509(CI95%:-0.689至-0.328,P值<0.001)。此外,发表偏倚的P值(双尾)指数分别为0.366和0.583,分别为Egger回归截距和Begg秩相关,分别。灵敏度的P值检测为0.003。使用MP2的细胞治疗程序可以潜在地减轻临床评分指数并纠正EAE动物恢复期的运动缺陷。在健康的老鼠中,大脑和髓鞘周围的神经元处于健康和生理状态(1)。为了评估人类的MS,有必要通过皮下注射CFA使用EAE程序在动物中模拟这种类型的疾病,MOG35-55,MT,还有Pert.因此,炎症和自身免疫发生,最终导致髓鞘破坏和运动症状(2)。通过抽吸骨髓中可用的祖细胞,MP2可以被分离和培养。通过激活这些类型的细胞,可以为细胞治疗过程准备丰富的MP2集合(3)。通过尾静脉注射或腹膜内注射后,这些细胞可以通过从BBB穿过而位于CNS中。它们开始抗炎活动并帮助修复受损的髓磷脂(4)。最终,临床症状可以得到很大改善,动物运动功能改善(5)。CFA,完全弗氏佐剂;MOG35-55,髓鞘少突胶质细胞糖蛋白;MT,结核分枝杆菌;Pert,百日咳;EAE,实验性自身免疫性脑脊髓炎;BM,骨髓;MP2,巨噬细胞M2;和BBB,血脑屏障.
Macrophage M2 (MP2)-based cell therapy is a novel medicinal treatment for animals with Experimental Autoimmune Encephalomyelitis (EAE) as an experimental model of multiple sclerosis (MS). This systematic review and meta-analysis study was designed to assess the overall therapeutic effects of MP2 cell therapy on Clinical Score and motor impairment in EAE-induced animals. All experiments on MP2 cell therapy in animals with EAE were gathered (by October 2, 2022) from English (PubMed, Scopus, WoS, Science Direct, and ISC) and Persian (MagIran and SID) databases. The searching strategy was designed using \"Experimental Autoimmune Encephalomyelitis,\" \"Multiple Sclerosis,\" and \"Macrophage M2\" keywords. Following primary and secondary screenings, eligible papers were selected based on the PRISMA 2020 guideline, and the study quality was assessed using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) checklist. The difference in means of Clinical Score (score 0-5) as the effect size (ES) was analyzed based on the random effect model (CMA software, v.2). Subgrouping (EAE phases of Onset, Peak, and Recovery) was applied, and I2 index was used to assess the heterogeneity index. Publication bias and sensitivity indices were also evaluated. P < 0.05 was considered significant, and the confidence interval (CI) was determined 95%. Among 22 gathered papers, medium to high quality studies were selected for meta-analysis. Difference in means, P value, and I2 for Onset, Peak, and Recovery phases were 0.082 (CI95%: -0.323-0.159, P value: 0.504, I2 : 67.961%), -0.606 (CI95%: -1.518 to -0.305, P value: 0.192, I2 : 96.070%), and -1.103 (CI95%: -1.390 to -0.816, P value: 0.000, I2 : 30.880%), respectively and Overall Effect was found -0.509 (CI95%: -0.689 to -0.328, P value < 0.001). Also, P value (two-tailed) indices for publication bias were 0.366 and 0.583 for Egger\'s regression intercept and Begg rank correlation, respectively. The P value for sensitivity was detected 0.003. Cell therapy procedure using MP2 can potentially alleviate the Clinical Scores Index and correct the motor defects in Recovery phase of EAE animals. In healthy mice, the brain and myelin surrounding neurons are in a healthy and physiological state (1). To evaluate MS in humans, it is necessary to model this type of disease in animals using EAE procedure through subcutaneous injection of CFA, MOG35-55 , MT, and Pert. Thus, inflammation and autoimmunity occur, which finally lead to myelin destruction and motor symptoms (2). By aspiration of progenitor cells available in bone marrow, the MP2 can be isolated and cultured. By activation of these types of cells, a rich collection of MP2 can be prepared for the cell-therapy process (3). After injection through the tail vein or intra-peritoneal procedure, these cells can be located in CNS through crossing from the BBB. They begin their anti-inflammatory activities and help repair the damaged myelin (4). Eventually, the clinical symptoms can be modified considerably, and the animal motor function improves (5). CFA, complete Freund\'s adjuvant; MOG35-55 , myelin oligodendrocyte glycoprotein; MT, Mycobacterium tuberculosis; Pert, pertussis; EAE, Experimental Autoimmune Encephalomyelitis; BM, bone marrow; MP2, macrophage M2; and BBB, blood brain barrier.