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Therapeutic Effects of Melatonin-Treated Bone Marrow Mesenchymal Stem Cells (BMSC) in a Rat Model of Alzheimer's Disease
Journal of Chemical Neuroanatomy ( IF 2.7 ) Pub Date : 2020-10-01 , DOI: 10.1016/j.jchemneu.2020.101804 Mahdi Ramezani 1 , Alireza Komaki 1 , Nasrin Hashemi-Firouzi 1 , Keywan Mortezaee 2 , Nafiseh Faraji 1 , Zoleikha Golipoor 3
Journal of Chemical Neuroanatomy ( IF 2.7 ) Pub Date : 2020-10-01 , DOI: 10.1016/j.jchemneu.2020.101804 Mahdi Ramezani 1 , Alireza Komaki 1 , Nasrin Hashemi-Firouzi 1 , Keywan Mortezaee 2 , Nafiseh Faraji 1 , Zoleikha Golipoor 3
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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.
中文翻译：
褪黑素处理的骨髓间充质干细胞 (BMSC) 对阿尔茨海默病大鼠模型的治疗作用
基于间充质干细胞（MSC）的治疗阿尔茨海默病（AD）越来越受到关注。然而，这方面的一个巨大挑战是MSCs移植后的低存活率。这项研究旨在通过褪黑激素 (MT) 预处理来改进基于骨髓间充质干细胞 (BM-MSC) 的治疗，褪黑激素 (MT) 是 AD 动物模型中的“已知抗氧化剂”。在本文中，我们从大鼠胫骨和股骨中分离出 BMSC，然后用 5μM MT 预处理细胞 24 小时。样本由 40 只雄性 Wistar 大鼠组成，随机分配为对照、假手术、MT 预处理的 BMSC 和淀粉样蛋白。 β(Aβ)肽BMSCs组。细胞移植后两个月进行新物体识别、Morris水迷宫、被动回避试验、旷场试验等多项测试。细胞治疗后69天处死大鼠，取出脑组织进行组织病理学分析，并对Beta微管蛋白、GFAP和iba1蛋白进行免疫组化分析。结果表明，静脉移植后MT-BMSCs和BMSCs均迁移至脑组织。然而，与BMSCs相比，MT-BMSCs对学习、认知和记忆的促进作用显着（P<<0.05）。此外，与MT-BMSCs相比，BMSCs中的GFAP和β微管蛋白显着升高，小胶质细胞显着下降。干细胞疗法已被提出作为神经退行性疾病的有效策略，但其治疗功能受到限制。研究表明，用褪黑激素预处理间充质干细胞可以部分提高细胞效率，从而减轻记忆和认知等 AD 并发症。
更新日期：2020-10-01
中文翻译：
褪黑素处理的骨髓间充质干细胞 (BMSC) 对阿尔茨海默病大鼠模型的治疗作用
基于间充质干细胞（MSC）的治疗阿尔茨海默病（AD）越来越受到关注。然而，这方面的一个巨大挑战是MSCs移植后的低存活率。这项研究旨在通过褪黑激素 (MT) 预处理来改进基于骨髓间充质干细胞 (BM-MSC) 的治疗，褪黑激素 (MT) 是 AD 动物模型中的“已知抗氧化剂”。在本文中，我们从大鼠胫骨和股骨中分离出 BMSC，然后用 5μM MT 预处理细胞 24 小时。样本由 40 只雄性 Wistar 大鼠组成，随机分配为对照、假手术、MT 预处理的 BMSC 和淀粉样蛋白。 β(Aβ)肽BMSCs组。细胞移植后两个月进行新物体识别、Morris水迷宫、被动回避试验、旷场试验等多项测试。细胞治疗后69天处死大鼠，取出脑组织进行组织病理学分析，并对Beta微管蛋白、GFAP和iba1蛋白进行免疫组化分析。结果表明，静脉移植后MT-BMSCs和BMSCs均迁移至脑组织。然而，与BMSCs相比，MT-BMSCs对学习、认知和记忆的促进作用显着（P<<0.05）。此外，与MT-BMSCs相比，BMSCs中的GFAP和β微管蛋白显着升高，小胶质细胞显着下降。干细胞疗法已被提出作为神经退行性疾病的有效策略，但其治疗功能受到限制。研究表明，用褪黑激素预处理间充质干细胞可以部分提高细胞效率，从而减轻记忆和认知等 AD 并发症。
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