Isik Sevim, Osman Sajeda, Yeman-Kiyak Bercem, Shamshir Suhair Rami Mohammed, Sanchez Nesrin Majdi Edwan
Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Uskudar University, Uskudar, Istanbul, Turkey.
Stem Cell Research and Application Center (USKOKMER), Uskudar University, Uskudar, Istanbul, Turkey.
CNS Neurosci Ther. 2025 Sep;31(9):e70577. doi: 10.1111/cns.70577.
This review provides a systematic evaluation of 94 stem cell clinical trials to treat neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease.
Data were collected from using relevant search terms, focusing exclusively on stem cell therapy. Of the 8000+ participants in these trials, nearly 70% were enrolled in AD-related studies. Only three Phase 3 studies were conducted, and most trials were in the early phases (Phases 1 and 2). Mesenchymal stem cells, neural stem cells, induced pluripotent stem cells, and embryonic stem cells are used the most to treat neurodegenerative diseases. This review also explores the emerging fields of preclinical and clinical investigations of stem cell-derived exosome-based therapies for neurodegenerative diseases.
Exosomes can cross the blood-brain barrier to deliver therapeutic molecules directly to the brain, offering a less invasive alternative to stem cell transplantation. Mesenchymal stem cell-derived exosomes, in particular, have demonstrated significant potential in preclinical models by reducing neuroinflammation, oxidative stress, and promoting neuronal regeneration. Additionally, recent advances in exosome engineering, including surface modifications, therapeutic agent loading, and transgenic modifications, have improved targeting, stability, blood-brain barrier delivery, and neural cell interactions, enabling targeted and effective treatment. Exosome-based therapies are in the preliminary phases of clinical investigation, with only three clinical trials.
Given the increasing interest in exosome therapy, clinical investigations are expected to increase. This growth will be driven by ongoing advancements in exosome technology, a deeper understanding of their therapeutic potential, and escalating demand for innovative treatment strategies for neurodegenerative diseases.
本综述对94项治疗神经退行性疾病的干细胞临床试验进行了系统评估，这些疾病包括阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和亨廷顿舞蹈症。
使用相关检索词收集数据，仅关注干细胞疗法。在这些试验的8000多名参与者中，近70%参与了与阿尔茨海默病相关的研究。仅进行了三项3期研究，大多数试验处于早期阶段（1期和2期）。间充质干细胞、神经干细胞、诱导多能干细胞和胚胎干细胞在治疗神经退行性疾病中使用最为频繁。本综述还探讨了基于干细胞衍生外泌体的神经退行性疾病治疗的临床前和临床研究的新兴领域。
外泌体可以穿过血脑屏障，将治疗分子直接递送至大脑，为干细胞移植提供了一种侵入性较小的替代方法。特别是间充质干细胞衍生的外泌体，在临床前模型中已通过减轻神经炎症、氧化应激和促进神经元再生显示出显著潜力。此外，外泌体工程的最新进展，包括表面修饰、治疗剂装载和转基因修饰，改善了靶向性、稳定性、血脑屏障递送和神经细胞相互作用，实现了靶向和有效的治疗。基于外泌体的疗法正处于临床研究的初步阶段，仅有三项临床试验。
鉴于对外泌体疗法的兴趣日益增加，预计临床研究将会增多。这种增长将由外泌体技术的不断进步、对其治疗潜力的更深入理解以及对神经退行性疾病创新治疗策略不断增长的需求所推动。
