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实验性立体定向海马细胞移植在阿尔茨海默病治疗中的潜力

Therapeutic Potential of Experimental Stereotactic Hippocampal Cell Transplant in the Management of Alzheimer's Disease.

作者信息

Agavriloaei Loredana Mariana, Iliescu Bogdan Florin, Pintilie Robert Mihai, Turliuc Dana Mihaela

机构信息

Department of Neurosurgery, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania.

Department of Neurosurgery, "Prof. Dr. N. Oblu" Emergency Clinical Hospital, 700309 Iasi, Romania.

出版信息

J Clin Med. 2025 Jan 29;14(3):891. doi: 10.3390/jcm14030891.

DOI:10.3390/jcm14030891
PMID:39941562
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11818268/
Abstract

Due to a continuous increase in life expectancy and the progress made in specialized healthcare, the incidence of Alzheimer's disease (AD) has dramatically increased to the point that it has become one of the main challenges of contemporary medicine. Despite a huge scientific and clinical effort, current treatments manage just a temporary alleviation of symptomatology but offer no cure. Modern trials involving cell transplantation in experimental animals require the involvement of neurosurgeons in the treatment protocol. CSF shunting, intraventricular infusions, or DBS for symptoms relief have been an integral part of the therapeutic arsenal from the very beginning. The development of stereotactic surgery has facilitated the experimental potential of cell transplantation in the hippocampus for Alzheimer's disease. We conducted a narrative review of the literature in the top three medical databases (PubMed, Science Direct, and Google Scholar) using the keywords "Alzheimer's disease", "hippocampus", and "transplant". After eliminating duplicates, 241 papers were selected and screened by title and abstract. Two reviewers independently analyzed the 88 papers and chose 32 experiments that involved stereotactic hippocampal transplantation of cells in experimental animals with AD. The stereotactic transplantation of cells such as mesenchymal stem cells (MSCs), neuronal stem cells (NSCs), induced pluripotent cells (iPSCs), astrocytes, and derivates from stem cells was analyzed. The experiments used either a chemically induced or transgenic AD model and observed the impact of the stereotactic transplantation with behavioral testing, MRS spectroscopy, and biochemical analysis. The stereotaxic method delivers minimal invasive treatment option by cell transplantation at the hippocampus. The results showed that amyloid deposits were lower after transplantation, showing a positive impact. Other impactful results involve proliferation of neurogenesis, downregulation of anti-inflammatory response, and increased neuronal plasticity. The increased precision with which the stereotaxic method manages to target deep structures of the brain and the results of the reviewed papers could represent an argument for future human trials. More studies are needed to confirm the viability of the transplanted cells and the long-term effects.

摘要

由于预期寿命的持续增长以及专业医疗保健取得的进展,阿尔茨海默病(AD)的发病率急剧上升,已成为当代医学面临的主要挑战之一。尽管在科学和临床方面付出了巨大努力,但目前的治疗方法只能暂时缓解症状,无法治愈。在实验动物中进行细胞移植的现代试验需要神经外科医生参与治疗方案。脑脊液分流、脑室内输注或用于缓解症状的深部脑刺激(DBS)从一开始就是治疗手段的重要组成部分。立体定向手术的发展促进了在海马体中进行细胞移植治疗阿尔茨海默病的实验潜力。我们使用关键词“阿尔茨海默病”“海马体”和“移植”,在前三大医学数据库(PubMed、Science Direct和谷歌学术)中对文献进行了叙述性综述。在剔除重复文献后,通过标题和摘要筛选出241篇论文。两位评审员独立分析了88篇论文,并选择了32项涉及在患有AD的实验动物中进行海马体立体定向细胞移植的实验。分析了间充质干细胞(MSC)、神经干细胞(NSC)、诱导多能干细胞(iPSC)、星形胶质细胞以及干细胞衍生物等细胞的立体定向移植。这些实验使用化学诱导或转基因AD模型,并通过行为测试、磁共振波谱(MRS)和生化分析观察立体定向移植的影响。立体定向方法通过在海马体进行细胞移植提供了微创治疗选择。结果表明,移植后淀粉样蛋白沉积减少,显示出积极影响。其他有意义的结果包括神经发生的增殖、抗炎反应的下调以及神经元可塑性的增加。立体定向方法能够精准靶向大脑深部结构的更高精度以及综述论文的结果可能为未来的人体试验提供依据。需要更多研究来证实移植细胞的可行性和长期效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15e7/11818268/d5eebac1c30d/jcm-14-00891-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15e7/11818268/1fab419de661/jcm-14-00891-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15e7/11818268/d5eebac1c30d/jcm-14-00891-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15e7/11818268/1fab419de661/jcm-14-00891-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15e7/11818268/d5eebac1c30d/jcm-14-00891-g002.jpg

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本文引用的文献

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Exploring neurosurgical interventions in Alzheimer's disease: current perspectives and future directions.探索阿尔茨海默病的神经外科干预:当前观点与未来方向
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