Department of Neurology, Faculty of Health Sciences, Medical University of Warsaw, 03-242 Warsaw, Poland.
Front Biosci (Landmark Ed). 2023 Oct 27;28(10):269. doi: 10.31083/j.fbl2810269.
Ischemic stroke is one of the major causes of death and disability. Since the currently used treatment option of reperfusion therapy has several limitations, ongoing research is focusing on the neuroprotective effects of microglia and stem cells. By exerting the bystander effect, secreting exosomes and forming biobridges, mesenchymal stem cells (MSCs), neural stem cells (NSCs), induced pluripotent stem cells (iPSCs), and multilineage-differentiating stress-enduring cells (Muse cells) have been shown to stimulate neurogenesis, angiogenesis, cell migration, and reduce neuroinflammation. Exosome-based therapy is now being extensively researched due to its many advantageous properties over cell therapy, such as lower immunogenicity, no risk of blood vessel occlusion, and ease of storage and modification. However, although preclinical studies have shown promising therapeutic outcomes, clinical trials have been associated with several translational challenges. This review explores the therapeutic effects of preconditioned microglia as well as various factors secreted in stem cell-derived extracellular vesicles with their mechanisms of action explained. Furthermore, an overview of preclinical and clinical studies is presented, explaining the main challenges of microglia and stem cell therapies, and providing potential solutions. In particular, a highlight is the use of novel stem cell therapy of Muse cells, which bypasses many of the conventional stem cell limitations. The paper concludes with suggestions for directions in future neuroprotective research.
缺血性中风是死亡和残疾的主要原因之一。由于目前使用的再灌注治疗选择有几个局限性，因此正在进行的研究集中在小胶质细胞和干细胞的神经保护作用上。间充质干细胞（MSCs）、神经干细胞（NSCs）、诱导多能干细胞（iPSCs）和多谱系分化应激耐受细胞（Muse 细胞）通过发挥旁观者效应、分泌外泌体和形成生物桥，被证明可以刺激神经发生、血管生成、细胞迁移，并减少神经炎症。由于外泌体治疗具有比细胞治疗更低的免疫原性、不存在血管阻塞的风险以及易于储存和修饰等诸多优势，因此目前正在广泛研究外泌体治疗。然而，尽管临床前研究显示出有希望的治疗效果，但临床试验与几个转化挑战有关。本综述探讨了预处理小胶质细胞以及干细胞衍生的细胞外囊泡中分泌的各种因子的治疗效果，并解释了它们的作用机制。此外，还介绍了临床前和临床研究的概述，解释了小胶质细胞和干细胞疗法的主要挑战，并提供了潜在的解决方案。特别是，强调了使用 Muse 细胞的新型干细胞疗法，该疗法绕过了许多传统干细胞的局限性。本文最后对未来神经保护研究的方向提出了建议。
