Systemic Transplantation Effect of Human Adipose Tissue Derived Mesenchymal Stem Cells on Cognitive Deficits and Hippocampal Antioxidant Capacity in Trimethyltin Model of Alzheimer's Disease

M. Edalatmanesh, Samireh Nemati, Habibollah Khodabandeh
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Abstract

Introduction: Stem cell-based therapies create new hope for the treatment of Alzheimer's disease (AD). Since the mesenchymal stem cells have neuroprotective and regeneration effects, this study aimed to investigate the memory, learning, and antioxidant capacity of the hippocampus following human adipose-derived mesenchymal stem cell (Ad-MSC) transplantation in Trimethyltin (TMT) rat's model of AD. Material & Methods: In total, 24 male Wistar rats were randomly divided into three groups (8 animals per group) of control (without any treatment), TMT+PBS (Trimethyltin+Phosphate buffer saline), and TMT+Ad-MSC (Trimethyltin+Stem cells). For the induction of the AD, TMT was peritoneally injected (8 mg/Kg). After 48 h, the TMT+Ad-MSC group received 1 million stem cells intravenously. One month after transplantation, avoidance and working memories were evaluated. Afterward, hippocampal levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and malondialdehyde (MDA) were measured using ELISA. Findings: The results showed a significant increase in the percentage of correct motor frequency in the Y maze, a decrease in the spent time in the dark room (P<0.05), and an increase in the latency time to the dark room in the TMT+Ad-MSC group, compared to the TMT+PBS group (P<0.01). Moreover, a significant increase in the CAT, SOD, and GPX enzymes activity, as well as a decrease in the MDA level in the hippocampus were observed in the TMT+Ad-MSC group, compared to the TMT+PBS group (P<0.05). Discussion & Conclusion: Xenotransplantation of human adipose tissue stem cell improved learning and memory, reduced tissue oxidative stress, and increased hippocampal antioxidant capacity in an animal model of AD.
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人脂肪组织来源间充质干细胞全身移植对阿尔茨海默病三甲基锡模型认知缺陷和海马抗氧化能力的影响
导读:干细胞疗法为治疗阿尔茨海默病(AD)创造了新的希望。由于间充质干细胞具有神经保护和再生作用,本研究旨在探讨人脂肪源性间充质干细胞(AD - msc)移植在Trimethyltin (TMT) AD大鼠模型中对海马记忆、学习和抗氧化能力的影响。材料与方法:选取24只雄性Wistar大鼠,随机分为对照组(未经任何处理)、TMT+PBS(三甲基锡+磷酸盐缓冲盐水)和TMT+Ad-MSC(三甲基锡+干细胞)3组(每组8只)。为了诱导AD,腹腔注射TMT (8 mg/Kg)。48 h后,TMT+Ad-MSC组静脉注射100万个干细胞。移植后1个月,评估回避和工作记忆。随后,采用ELISA法测定海马超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPX)和丙二醛(MDA)水平。结果显示:与TMT+PBS组相比,TMT+Ad-MSC组在Y迷宫中正确运动频率的百分比显著增加,在暗室中度过的时间显著减少(P<0.05),到暗室的潜伏期显著增加(P<0.01)。与TMT+PBS组相比,TMT+Ad-MSC组海马组织中CAT、SOD、GPX酶活性显著升高,MDA水平显著降低(P<0.05)。讨论与结论:在AD动物模型中,人脂肪组织干细胞异种移植改善了学习和记忆,减少了组织氧化应激,增加了海马抗氧化能力。
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