Therapeutic effects of melatonin-treated bone marrow mesenchymal stem cells (BMSC) in a rat model of Alzheimer's disease
Therapeutic effects of melatonin-treated bone marrow mesenchymal stem cells (BMSC) in a rat model of Alzheimer's disease
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DOI：
10.1016/j.jchemneu.2020.101804
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发表时间：
2020-10-01
影响因子：
2.8
通讯作者：
Golipoor, Zoleikha
中科院分区：
文献类型：
--
作者：
Ramezani, Mahdi;Komaki, Alireza;Golipoor, Zoleikha
基于间充质干细胞（mesenchymal stem cells，MSCs）的治疗阿尔茨海默病（Alzheimer's disease，AD）的研究越来越受到重视。然而，在这方面的一个巨大挑战是MSC移植后的低存活率。本研究旨在通过褪黑激素（MT）预处理改善基于骨髓间充质干细胞（BM-MSCs）的治疗，褪黑激素是AD动物模型中的“已知抗氧化剂”。本研究从大鼠胫骨和股骨中分离骨髓间充质干细胞，用5 μ M MT预处理24 h，将40只雄性Wistar大鼠随机分为对照组、假手术组、MT预处理组和淀粉样β（A β）肽BMSCs组，细胞移植后2个月进行新物体识别、Morris水迷宫、被动回避实验、并进行了旷场试验。结果表明，MT-BMSCs和BMSCs经静脉移植后均能向脑组织内迁移，但MT-BMSCs对大鼠学习、认知和记忆能力的促进作用明显优于BMSCs（P < 0.05）。此外，与MT-BMSCs相比，BMSCs中GFAP和β微管蛋白的表达显著升高，而小胶质细胞的表达显著下降。干细胞治疗已被提出作为治疗神经退行性疾病的有效策略，但其治疗功能受到限制。
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) pretreatment, 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 5 mu M 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 (A beta) 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.