Xiong Wei, Liu Ye, Zhou Heng, Jing Shuili, He Yan, Ye Qingsong
Center of Regenerative Medicine, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China.
Institute of Regenerative and Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China.
Front Cell Dev Biol. 2022 Sep 15;10:999024. doi: 10.3389/fcell.2022.999024. eCollection 2022.
Alzheimer's disease (AD) is a destructive neurodegenerative disease with the progressive dysfunction, structural disorders and decreased numbers of neurons in the brain, which leads to long-term memory impairment and cognitive decline. There is a growing consensus that the development of AD has several molecular mechanisms similar to those of other neurodegenerative diseases, including excessive accumulation of misfolded proteins and neurotoxic substances produced by hyperactivated microglia. Nonetheless, there is currently a lack of effective drug candidates to delay or prevent the progression of the disease. Based on the excellent regenerative and reparative capabilities of stem cells, the application of them to repair or replace injured neurons carries enormous promise. Dental pulp stem cells (DPSCs), originated from ectomesenchyme of the cranial neural crest, hold a remarkable potential for neuronal differentiation, and additionally express a variety of neurotrophic factors that contribute to a protective effect on injured neuronal cells. Notably, DPSCs can also express immunoregulatory factors to control neuroinflammation and potentiate the regeneration and recovery of injured neurons. These extraordinary features along with accessibility make DPSCs an attractive source of postnatal stem cells for the regeneration of neurons or protection of existing neural circuitry in the neurodegenerative diseases. The present reviews the latest research advance in the pathophysiology of AD and elaborate the neurodifferentiation and neuroprotective properties of DPSCs as well as their application prospects in AD.
阿尔茨海默病（AD）是一种具有破坏性的神经退行性疾病，其特征为大脑中神经元功能逐渐失调、结构紊乱以及数量减少，进而导致长期记忆障碍和认知能力下降。越来越多的共识认为，AD的发展具有与其他神经退行性疾病相似的多种分子机制，包括错误折叠蛋白的过度积累以及过度活化的小胶质细胞产生的神经毒性物质。尽管如此，目前仍缺乏有效的候选药物来延缓或阻止该疾病的进展。基于干细胞出色的再生和修复能力，将其应用于修复或替代受损神经元具有巨大的前景。牙髓干细胞（DPSCs）起源于颅神经嵴的外胚间充质，具有显著的神经元分化潜力，此外还表达多种神经营养因子，对受损神经元细胞具有保护作用。值得注意的是，DPSCs还能表达免疫调节因子以控制神经炎症，并增强受损神经元的再生和恢复。这些非凡特性以及其易获取性，使得DPSCs成为用于神经退行性疾病中神经元再生或保护现有神经回路的极具吸引力的产后干细胞来源。本综述阐述了AD病理生理学的最新研究进展，详细介绍了DPSCs的神经分化和神经保护特性及其在AD中的应用前景。
