Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
J Chem Neuroanat. 2020 Oct;108:101804. doi: 10.1016/j.jchemneu.2020.101804. Epub 2020 May 26.
The therapy based on mesenchymal stem cells(MSCs) has received growing attraction for Alzheimer's disease(AD). However, a great challenge in this regard is the low survival rate of MSCs following transplantation. This study seeks to improve the therapy based on Bone Marrow MSCs (BM-MSCs) through melatonin (MT) pre-treatment, which is 'a known antioxidant' in an animal model of AD. In this paper, we separated BMSCs from the rat tibia and femur bones and then pretreated cells were with 5μM of MT for 24 h.The sample consisted of 40 male Wistar rats randomly assigned to the control, sham,MT-pretreated BMSCs and amyloid-beta (Aβ) peptide BMSCs groups.Two months after the cell transplantation,a number of tests including novel object recognition, Morris water maze, passive avoidance test, and open field test were undertaken. 69 days after the cell therapy,the rats were sacrificed.We removed brain tissues histopathological analysis and carried out immunohistochemistry for Beta tubulin, GFAP and iba1 proteins.The results suggested that both MT-BMSCs and BMSCs moved to brain tissues following the intravenous transplantation.However,MT-BMSCs had a significant effect on boosting learning, cognition and memory in comparison with BMSCs (P < 0.05). Furthermore, there was a significant rise in GFAP and Beta tubulin and substantial fall in microglial cells in the BMSCs in comparison with MT-BMSCs.Stem cell therapy has been proposed as an effective strategy for neurodegenerative diseases,but its therapeutic features are restricted.It has been shown that the pretreatment of MSCs with melatonin partly would boost cells efficiency and thereby alleviate AD complications such as memory and cognition.
基于间充质干细胞（MSCs）的治疗方法已经引起了阿尔茨海默病（AD）的关注。然而，在这方面的一个巨大挑战是移植后 MSC 的存活率低。本研究旨在通过褪黑素（MT）预处理来改善基于骨髓间充质干细胞（BM-MSCs）的治疗方法，MT 是 AD 动物模型中“已知的抗氧化剂”。在本文中，我们从大鼠胫骨和股骨中分离出 BMSCs，然后用 5μM 的 MT 预处理细胞 24 小时。样本由 40 只雄性 Wistar 大鼠组成，随机分为对照组、假手术组、MT 预处理 BMSCs 组和淀粉样β（Aβ）肽 BMSCs 组。细胞移植后两个月，进行了新物体识别、Morris 水迷宫、被动回避试验和旷场试验等多项测试。细胞治疗 69 天后，处死大鼠。我们取出脑组织进行组织病理学分析，并进行 Beta 微管蛋白、GFAP 和 iba1 蛋白的免疫组织化学分析。结果表明，MT-BMSCs 和 BMSCs 经静脉移植后均能转移到脑组织中。然而，与 BMSCs 相比，MT-BMSCs 对促进学习、认知和记忆有显著效果（P<0.05）。此外，与 MT-BMSCs 相比，BMSCs 中的 GFAP 和 Beta 微管蛋白显著增加，小胶质细胞显著减少。干细胞治疗已被提议作为治疗神经退行性疾病的有效策略，但它的治疗效果受到限制。研究表明，MT 预处理 MSC 可在一定程度上提高细胞效率，从而减轻 AD 并发症，如记忆和认知。
