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牙间充质干细胞在阿尔茨海默病中的治疗应用——一项范围综述

Therapeutic Applications of Dental Mesenchymal Stem Cells in Alzheimer's Disease-A Scoping Review.

作者信息

Agnihotri Rupali, Gaur Sumit

机构信息

Department of Periodontology, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education (MAHE), Udupi 576104, India.

Department of Pedodontics and Preventive Dentistry, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education (MAHE), Udupi 576104, India.

出版信息

Dent J (Basel). 2025 Jun 26;13(7):288. doi: 10.3390/dj13070288.

DOI:10.3390/dj13070288
PMID:40710133
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12293466/
Abstract

BACKGROUND/OBJECTIVES: Alzheimer's disease (AD), a neurodegenerative condition, produces dementia and cognitive debility. Lately, preclinical models of AD have shown neuroregenerative potential of mesenchymal stem cells of dental origin (DMSC). This scoping review aims to map and synthesize the evidence on the therapeutic applications of DMSCs in AD management.

METHODS

This review followed the Arksey and O'Malley framework for scoping reviews and PRISMA-ScR guidelines. Scopus, Medline (Pubmed), Web of Science, and Embase databases were searched for published literature until February 2025. Data was mapped according to the type of DMSC and their therapeutic properties useful in AD management, like neuro differentiation, neuroprotection through increased neuron number and vitality, anti-neuroinflammation, mitochondrial repair, and improved cognition.

RESULTS

A total of 22 articles were included. A research gap existed, as most studies were preclinical (in vitro and animal models) with no clinical trials in humans. Furthermore, they mostly evaluated neuroregenerative properties of dental pulp stem cells (DPSC) and stem cells from human-exfoliated deciduous teeth (SHED), while Periodontal ligament stem cells (PDLSC) were least studied. All the DMSCs were neuroprotective and increased neuron number and vitality. Neurodifferentiation was reported in DPSCs and PDLSCs, while DPSCs and SHEDs showed anti-neuroinflammation, mitochondrial repair, and improved cognition in AD animal models.

CONCLUSIONS

Although the DPSCs and SHEDs showed promising outcomes in preclinical models of AD, a gap exists as results have not been translated into human clinical trials. Future advances may identify plausible ways of applying the DMSCs to regain the lost neurons and re-establish a healthy brain microenvironment.

摘要

背景/目的:阿尔茨海默病(AD)是一种神经退行性疾病,会导致痴呆和认知功能衰退。最近,AD的临床前模型显示了牙源性间充质干细胞(DMSC)的神经再生潜力。本综述旨在梳理和综合关于DMSC在AD治疗应用方面的证据。

方法

本综述遵循Arksey和O'Malley的综述框架以及PRISMA-ScR指南。检索了Scopus、Medline(PubMed)、Web of Science和Embase数据库,以获取截至2025年2月发表的文献。根据DMSC的类型及其在AD治疗中的治疗特性进行数据梳理,这些特性包括神经分化、通过增加神经元数量和活力实现神经保护、抗神经炎症、线粒体修复以及改善认知。

结果

共纳入22篇文章。存在研究空白,因为大多数研究是临床前研究(体外和动物模型),尚无人体临床试验。此外,这些研究大多评估了牙髓干细胞(DPSC)和人脱落乳牙干细胞(SHED)的神经再生特性,而对牙周膜干细胞(PDLSC)的研究最少。所有DMSC都具有神经保护作用,并增加了神经元数量和活力。DPSC和PDLSC有神经分化的报道,而DPSC和SHED在AD动物模型中显示出抗神经炎症、线粒体修复以及改善认知的作用。

结论

尽管DPSC和SHED在AD临床前模型中显示出了有前景的结果,但仍存在差距,因为这些结果尚未转化为人体临床试验。未来的进展可能会找到应用DMSC来恢复丢失的神经元并重建健康脑微环境的可行方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a88/12293466/031f86a6f770/dentistry-13-00288-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a88/12293466/f37c893ab218/dentistry-13-00288-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a88/12293466/031f86a6f770/dentistry-13-00288-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a88/12293466/f37c893ab218/dentistry-13-00288-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a88/12293466/031f86a6f770/dentistry-13-00288-g005.jpg

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本文引用的文献

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Clinical-grade human dental pulp stem cells improve adult hippocampal neural regeneration and cognitive deficits in Alzheimer's disease.临床级人牙髓干细胞可改善阿尔茨海默病中的成年海马神经再生和认知缺陷。
Theranostics. 2025 Jan 1;15(3):894-914. doi: 10.7150/thno.102315. eCollection 2025.
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Recent Advances in Regenerative Endodontics: A Review of Current Techniques and Future Directions.再生牙髓病学的最新进展:当前技术与未来方向综述
Cureus. 2024 Nov 20;16(11):e74121. doi: 10.7759/cureus.74121. eCollection 2024 Nov.
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Dental pulp stem cells - A basic research and future application in regenerative medicine.
牙髓干细胞——再生医学中的基础研究与未来应用。
Biomed Pharmacother. 2024 Sep;178:116990. doi: 10.1016/j.biopha.2024.116990. Epub 2024 Jul 17.
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Human dental pulp stem cells mitigate the neuropathology and cognitive decline via AKT-GSK3β-Nrf2 pathways in Alzheimer's disease.人牙髓间充质干细胞通过 AKT-GSK3β-Nrf2 通路减轻阿尔茨海默病的神经病理学和认知衰退。
Int J Oral Sci. 2024 May 13;16(1):40. doi: 10.1038/s41368-024-00300-4.
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Addressing the Discrepancies Between Animal Models and Human Alzheimer's Disease Pathology: Implications for Translational Research.解决动物模型与人类阿尔茨海默病病理学之间的差异:对转化研究的影响。
J Alzheimers Dis. 2024;98(4):1199-1218. doi: 10.3233/JAD-240058.
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Alzheimer's disease current therapies, novel drug delivery systems and future directions for better disease management.阿尔茨海默病的现有疗法、新型药物传递系统以及更好疾病管理的未来方向。
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