He Cong, Chen Baojiang, Yan Ciai, Zhou Xiaoqing
Second Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China.
First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China.
Front Genome Ed. 2025 Aug 26;7:1612868. doi: 10.3389/fgeed.2025.1612868. eCollection 2025.
Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by Aβ plaques, tau protein neuronal fiber tangles, and neuroinflammation, poses a significant global health problem, and current therapies focus on the symptoms rather than the cause. This paper gives a new multidimensional therapeutic form to AD treatment by exploring the integrated application of stem cell therapy and CRISPR/Cas9 gene editing technology. The study comprehensively dissected the roles of neural stem cells (NSCs), induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) in neural replacement, neuroinflammation modulation and neuroplasticity enhancement, and also explored the application of CRISPR/Cas9 in modifying the pathogenic variants of AD-related genes (APP, PSEN1 and PSEN2). The key findings suggest that gene-edited iPSCs can reduce abnormal Aβ and tau protein accumulation in AD models, improve cognitive function, and provide a platform for disease modeling and drug screening. Stem cell transplantation promotes neurogenesis and synaptic plasticity by secreting neurotrophic factors to improve the brain microenvironment. Despite the challenges of off-target effects, immune rejection, and long-term safety, the synergistic application of these two technologies offers a breakthrough solution for AD treatment. This paper highlights the translational potential of combining stem cells with gene editing technology, which is expected to drive clinical applications in the next 5-10 years. The integration of these advanced technologies not only addresses the limitations of current AD treatments, but also paves the way for a personalized medical approach that is expected to revolutionize the AD treatment landscape and bring new hope to patients worldwide.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,其特征为β淀粉样蛋白(Aβ)斑块、tau蛋白神经元纤维缠结和神经炎症,是一个重大的全球健康问题,目前的治疗方法侧重于症状而非病因。本文通过探索干细胞疗法和CRISPR/Cas9基因编辑技术的综合应用,为AD治疗提供了一种新的多维治疗形式。该研究全面剖析了神经干细胞(NSCs)、诱导多能干细胞(iPSCs)和间充质干细胞(MSCs)在神经替代、神经炎症调节和神经可塑性增强中的作用,还探索了CRISPR/Cas9在修饰AD相关基因(APP、PSEN1和PSEN2)的致病变体中的应用。关键研究结果表明,基因编辑的iPSCs可以减少AD模型中异常Aβ和tau蛋白的积累,改善认知功能,并为疾病建模和药物筛选提供一个平台。干细胞移植通过分泌神经营养因子促进神经发生和突触可塑性,以改善脑微环境。尽管存在脱靶效应、免疫排斥和长期安全性等挑战,但这两种技术的协同应用为AD治疗提供了一个突破性的解决方案。本文强调了将干细胞与基因编辑技术相结合的转化潜力,预计在未来5至10年内推动临床应用。这些先进技术的整合不仅解决了当前AD治疗的局限性,还为个性化医疗方法铺平了道路,有望彻底改变AD治疗格局,为全球患者带来新希望。