Revilla Gusti, Ali Hirowati
Doctoral Program Biomedical Science, Faculty of Medicine, Andalas University, Padang, Indonesia.
Department of Medical Laboratory Technology, STIKES Syedza Saintika, Indonesia.
Iran J Med Sci. 2024 Jul 1;49(7):441-449. doi: 10.30476/ijms.2023.98912.3104. eCollection 2024 Jul.
Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual cognitive impairment, including loss of synapses and nerve cells involved in learning, memory, and habit formation processes. Bone Marrow Mesenchymal Stem Cells (BM-MSCs) are multipotent cells. Because of their self-renewable, differentiation, and immunomodulatory capabilities, they are commonly used to treat many disorders. Hence, the current study intends to examine the effect of BM-MSCs transplantation on Aluminum chloride (AlCl)-induced cognitive problems, an experimental model resembling AD's hallmarks in rats.
The study was conducted in 2022 at The Biomedical Laboratory Faculty of Medicine, Andalas University, Indonesia. Adult male Wistar rats (three groups: negative control; no intervention+treatment with PBS; positive control: AlCl+treatment with aqua dest; AlCl+BM-MSCs: AlCl+treatment with BM-MSCs, n=5 each) were treated daily with AlCl orally for five days. Stem cells were intraperitoneally injected into rats at a dose of 1x10 cells/rat. The same quantity of phosphate-buffered saline was given to the control group. One month after stem cell injection, the rat brain tissue was removed and placed in the film bottles that had been created. The expression of neural progenitor cell markers, including nestin and sex-determining Y-box 2 (SOX-2), was analyzed using real-time polymerase chain reaction (RT-PCR). Rats' cognitive and functional memory were examined using Y-maze. Data were analyzed using SPSS software (version 26.0) with a one-way analysis of variance (ANOVA) test.
The gene expression of nestin (29.74±0.42), SOX-2 (31.44±0.67), and percent alternation of Y-maze (67.04±2.28) increased in the AlCl+BM-MSCs group compared to that in the positive control group. RT-PCR analysis indicated that nestin (P<0.001) and SOX-2 (P<0.001) were significantly enhanced in the AlCl+BM-MSCs group compared to the positive control group. This group also indicated an increased percent alternation of Y-maze (P<0.001) in the AlCl+BM-MSCs group compared to the positive control group.
Due to its potential effects on cell therapy, BM-MSCs were found effective in a rat model of AD on the impairment of the rats' behavior and increased expression of neural progenitor cell markers.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征为逐渐出现认知障碍，包括参与学习、记忆和习惯形成过程的突触和神经细胞丧失。骨髓间充质干细胞（BM-MSCs）是多能细胞。由于其自我更新、分化和免疫调节能力，它们常用于治疗多种疾病。因此，本研究旨在探讨BM-MSCs移植对氯化铝（AlCl）诱导的认知问题的影响，该实验模型类似于大鼠AD的特征。
该研究于2022年在印度尼西亚安达拉大学医学院生物医学实验室进行。成年雄性Wistar大鼠（三组：阴性对照；无干预+用PBS治疗；阳性对照：AlCl+用蒸馏水治疗；AlCl+BM-MSCs：AlCl+用BM-MSCs治疗，每组n = 5）每天口服AlCl，持续五天。以1x10个细胞/只大鼠的剂量将干细胞腹腔注射到大鼠体内。给对照组注射相同量的磷酸盐缓冲盐水。干细胞注射一个月后，取出大鼠脑组织并放入已制备好的薄膜瓶中。使用实时聚合酶链反应（RT-PCR）分析神经祖细胞标志物的表达，包括巢蛋白和性别决定Y盒2（SOX-2）。使用Y迷宫检测大鼠的认知和功能性记忆。使用SPSS软件（版本26.0）进行单因素方差分析（ANOVA）检验来分析数据。
与阳性对照组相比，AlCl+BM-MSCs组中巢蛋白的基因表达（29.74±0.42）、SOX-2的基因表达（31.44±0.67）以及Y迷宫的交替百分比（67.04±2.28）均增加。RT-PCR分析表明，与阳性对照组相比，AlCl+BM-MSCs组中巢蛋白（P<0.001）和SOX-2（P<0.001）显著增强。与阳性对照组相比，该组还表明AlCl+BM-MSCs组中Y迷宫的交替百分比增加（P<0.001）。
由于其对细胞治疗的潜在作用，发现BM-MSCs在AD大鼠模型中对大鼠行为损伤和神经祖细胞标志物表达增加有效。
