Campos Henrique C, Ribeiro Deidiane Elisa, Hashiguchi Debora, Hukuda Deborah Y, Gimenes Christiane, Romariz Simone A A, Ye Qing, Tang Yong, Ulrich Henning, Longo Beatriz Monteiro
Laboratório de Neurofisiologia, Depto. Fisiologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, SP, Brazil.
Stem Cell Rev Rep. 2022 Feb;18(2):781-791. doi: 10.1007/s12015-021-10321-9. Epub 2022 Jan 8.
Alzheimer's disease (AD) is a severe disabling condition with no cure currently available, which accounts for 60-70% of all dementia cases worldwide. Therefore, the investigation of possible therapeutic strategies for AD is necessary. To this end, animal models corresponding to the main aspects of AD in humans have been widely used. Similar to AD patients, the double transgenic APPswe/PS1dE9 (APP/PS1) mice show cognitive deficits, hyperlocomotion, amyloid-β (Αβ) plaques in the cortex and hippocampus, and exacerbated inflammatory responses. Recent studies have shown that these neuropathological features could be reversed by stem cell transplantation. However, the effects induced by neural (NSC) and mesenchymal (MSC) stem cells has never been compared in an AD animal model. Therefore, the present study aimed to investigate whether transplantation of NSC or MSC into the hippocampus of APP/PS1 mice reverses AD-induced pathological alterations, evaluated by the locomotor activity (open field test), short- and long-term memory (object recognition) tests, Αβ plaques (6-E10), microglia distribution (Iba-1), M1 (iNOS) and M2 (ARG-1) microglial phenotype frequencies. NSC and MSC engraftment reduced the number of Αβ plaques and produced an increase in M2 microglia polarization in the hippocampus of APP/PS1 mice, suggesting an anti-inflammatory effect of stem cell transplantation. NSC also reversed the hyperlocomotor activity and increased the number of microglia in the hippocampus of APP/PS1 mice. No impairment of short or long-term memory was observed in APP/PS1 mice. Overall, this study highlights the potential beneficial effects of transplanting NSC or MSC for AD treatment.
阿尔茨海默病（AD）是一种严重的致残性疾病，目前尚无治愈方法，在全球所有痴呆病例中占60 - 70%。因此，有必要研究AD可能的治疗策略。为此，与人类AD主要方面相对应的动物模型已被广泛使用。与AD患者相似，双转基因APPswe/PS1dE9（APP/PS1）小鼠表现出认知缺陷、活动亢进、皮质和海马中的β淀粉样蛋白（Aβ）斑块以及加剧的炎症反应。最近的研究表明，这些神经病理学特征可通过干细胞移植得到逆转。然而，在AD动物模型中，从未比较过神经干细胞（NSC）和间充质干细胞（MSC）所诱导的效果。因此，本研究旨在探究将NSC或MSC移植到APP/PS1小鼠海马中是否能逆转AD诱导的病理改变，并通过运动活动（旷场试验）、短期和长期记忆（物体识别）试验、Aβ斑块（6 - E10）、小胶质细胞分布（Iba - 1）、M1（诱导型一氧化氮合酶）和M2（精氨酸酶 - 1）小胶质细胞表型频率进行评估。NSC和MSC的植入减少了APP/PS1小鼠海马中Aβ斑块的数量，并使M2小胶质细胞极化增加，提示干细胞移植具有抗炎作用。NSC还逆转了APP/PS1小鼠的活动亢进，并增加了其海马中小胶质细胞的数量。在APP/PS1小鼠中未观察到短期或长期记忆受损。总体而言，本研究突出了移植NSC或MSC对AD治疗的潜在有益作用。
