Department of Genetics, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Department of Physiology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Behav Brain Res. 2023 Aug 24;452:114543. doi: 10.1016/j.bbr.2023.114543. Epub 2023 Jun 11.
Alzheimer's disease (AD), a prevalent progressive neurodegenerative disease, is mainly characterized by dementia, memory loss, and cognitive disorder. Rising research was performed to develop pharmacological or non-pharmacological approaches to treat or improve AD complications. Mesenchymal stem cells (MSCs) are stromal cells that can self-renew and exhibit multilineage differentiation. Recent evidence suggested that some of the therapeutic effects of MSCs are mediated by the secreted paracrine factors. These paracrine factors, called MSC- conditioned medium (MSC-CM), may stimulate endogenous repair, promote angio- and artery genesis, and reduce apoptosis through paracrine mechanisms. The current study aims to systematically review the advantages of MSC-CM to the development of research and therapeutic concepts for AD management.
The present systematic review was performed using PubMed, Web of Science, and Scopus from April 2020 to May 2022 following the "Preferred Reporting Items for Systematic Reviews" (PRISMA) guidelines. The keywords, including "Conditioned medium OR Conditioned media OR Stem cell therapy" AND "Alzheimer's," was searched, and finally, 13 papers were extracted.
The obtained data revealed that MSC-CMs might positively affect neurodegenerative diseases prognosis, especially AD, through various mechanisms, including a decrease in neuro-inflammation, reduction of oxidative stress and Aβ formation, modulation of Microglia function and count, reduction of apoptosis, induction of synaptogenesis and neurogenesis. Also, the results showed that MSC-CM administration could significantly improve cognitive and memory function, increase the expression of neurotrophic factors, decrease the production of pro-inflammatory cytokines, improve mitochondrial function, reduce cytotoxicity, and increase neurotransmitter levels.
While inhibiting the induction of neuroinflammation could be considered the first therapeutic effect of CMs, the prevention of apoptosis could be regarded as the most crucial effect of CMs on AD improvement.
阿尔茨海默病(AD)是一种常见的进行性神经退行性疾病,主要表现为痴呆、记忆丧失和认知障碍。目前正在进行大量研究,以开发治疗或改善 AD 并发症的药理学或非药理学方法。间充质干细胞(MSCs)是一种基质细胞,具有自我更新和多能分化的能力。最近的证据表明,MSCs 的一些治疗效果是通过分泌的旁分泌因子介导的。这些旁分泌因子,称为 MSC 条件培养基(MSC-CM),可能通过旁分泌机制刺激内源性修复、促进血管生成和动脉生成以及减少细胞凋亡。本研究旨在系统地综述 MSC-CM 在 AD 管理的研究和治疗概念发展中的优势。
本系统评价按照“系统评价和荟萃分析优先报告的项目”(PRISMA)指南,使用 PubMed、Web of Science 和 Scopus 从 2020 年 4 月至 2022 年 5 月进行了检索。使用的关键词包括“条件培养基 OR 条件培养基 OR 干细胞治疗”和“阿尔茨海默病”,最终提取了 13 篇论文。
获得的数据表明,MSC-CM 通过多种机制可能对神经退行性疾病的预后产生积极影响,特别是 AD,包括减少神经炎症、减少氧化应激和 Aβ形成、调节小胶质细胞功能和数量、减少细胞凋亡、诱导突触发生和神经发生。此外,结果还表明,MSC-CM 给药可显著改善认知和记忆功能,增加神经营养因子的表达,减少促炎细胞因子的产生,改善线粒体功能,降低细胞毒性,增加神经递质水平。
虽然抑制神经炎症的诱导可以被认为是 CMs 的第一个治疗效果,但预防细胞凋亡可以被认为是 CMs 对 AD 改善最重要的作用。