Honda Taishi, Kawabori Masahito, Fujimura Miki
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Hokkaido, Japan.
Int J Mol Sci. 2025 Jul 31;26(15):7405. doi: 10.3390/ijms26157405.
Central nervous system (CNS) disorders present significant therapeutic challenges due to the limited regenerative capacity of neural tissues, resulting in long-term disability for many patients. Consequently, the development of novel therapeutic strategies is urgently warranted. Stem cell therapies show considerable potential for mitigating brain damage and restoring neural connectivity, owing to their multifaceted properties, including anti-apoptotic, anti-inflammatory, neurogenic, and vasculogenic effects. Recent research has also identified exosomes-small vesicles enclosed by a lipid bilayer, secreted by stem cells-as a key mechanism underlying the therapeutic effects of stem cell therapies, and given their enhanced stability and superior blood-brain barrier permeability compared to the stem cells themselves, exosomes have emerged as a promising alternative treatment for CNS disorders. A key challenge in the application of both stem cell and exosome-based therapies for CNS diseases is the method of delivery. Currently, several routes are being investigated, including intracerebral, intrathecal, intravenous, intranasal, and intra-arterial administration. Intracerebral injection can deliver a substantial quantity of stem cells directly to the brain, but it carries the potential risk of inducing additional brain injury. Conversely, intravenous transplantation is minimally invasive but results in limited delivery of cells and exosomes to the brain, which may compromise the therapeutic efficacy. With advancements in catheter technology, intra-arterial administration of stem cells and exosomes has garnered increasing attention as a promising delivery strategy. This approach offers the advantage of delivering a significant number of stem cells and exosomes to the brain while minimizing the risk of additional brain damage. However, the investigation into the therapeutic potential of intra-arterial transplantation for CNS injury is still in its early stages. In this comprehensive review, we aim to summarize both basic and clinical research exploring the intra-arterial administration of stem cells and exosomes for the treatment of CNS diseases. Additionally, we will elucidate the underlying therapeutic mechanisms and provide insights into the future potential of this approach.
由于神经组织的再生能力有限，中枢神经系统（CNS）疾病带来了重大的治疗挑战，导致许多患者长期残疾。因此，迫切需要开发新的治疗策略。干细胞疗法因其多方面的特性，包括抗凋亡、抗炎、神经生成和血管生成作用，在减轻脑损伤和恢复神经连接方面显示出巨大潜力。最近的研究还发现，外泌体——由干细胞分泌的被脂质双层包裹的小囊泡——是干细胞疗法治疗效果的关键机制，并且与干细胞本身相比，外泌体具有更高的稳定性和更好的血脑屏障通透性，已成为治疗中枢神经系统疾病的一种有前景的替代疗法。将基于干细胞和外泌体的疗法应用于中枢神经系统疾病的一个关键挑战是给药方法。目前，正在研究几种途径，包括脑内、鞘内、静脉内、鼻内和动脉内给药。脑内注射可以将大量干细胞直接输送到大脑，但存在诱发额外脑损伤的潜在风险。相反，静脉移植微创，但导致细胞和外泌体向大脑的递送有限，这可能会影响治疗效果。随着导管技术的进步，动脉内注射干细胞和外泌体作为一种有前景的递送策略越来越受到关注。这种方法的优点是在将大量干细胞和外泌体输送到大脑的同时，将额外脑损伤的风险降至最低。然而，动脉内移植治疗中枢神经系统损伤的治疗潜力研究仍处于早期阶段。在这篇全面的综述中，我们旨在总结探索动脉内注射干细胞和外泌体治疗中枢神经系统疾病的基础研究和临床研究。此外，我们将阐明潜在的治疗机制，并深入探讨这种方法的未来潜力。
