Kato Yuya, Aburakawa Daiki, Tashiro Ryosuke, Zhou Yuan, Rashad Sherif, Endo Hidenori, Tominaga Teiji, Niizuma Kuniyasu
Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Neurosurgical Engineering and Translational Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan.
J Cereb Blood Flow Metab. 2025 Mar;45(3):542-557. doi: 10.1177/0271678X241290363. Epub 2024 Oct 13.
Ischemic stroke is a leading cause of disability and death globally. Stem cell therapies are emerging as a frontier for enhancing post-stroke recovery, with Muse cells-a subclass of pluripotent stem cells-demonstrating considerable promise. Muse cells are notable not only for their potential in cell replacement but also for their role in modulating immune responses following cerebral infarction. In the present study, we administered Muse cells intravenously to mice after inducing a stroke via distal middle cerebral artery occlusion. We evaluated motor outcomes, splenocyte populations, cytokine profiles, and gene expression 2 weeks after inducing stroke. Additionally, comparisons were drawn between outcomes in splenectomized mice and those receiving adoptive splenocyte transfer to discern the specific influence of the spleen on treatment efficacy. Our findings revealed that Muse cell therapy facilitates motor recovery, an effect that is compromised in the absence of the spleen. Spleens in treated mice exhibited a shift in neutrophil counts, increased cytokine activity, and a notable uptick in the expression of genes related to protein folding. These insights affirm the potential therapeutic effect of Muse cells in post-stroke treatment strategies, with their efficacy attributed, at least in part, to immunomodulatory pathways involving the spleen.
缺血性中风是全球致残和死亡的主要原因。干细胞疗法正在成为促进中风后恢复的前沿领域，其中多能干细胞的一个亚类——多潜能非对称分裂细胞（Muse细胞）显示出巨大的潜力。Muse细胞不仅因其在细胞替代方面的潜力而引人注目，还因其在脑梗死免疫反应调节中的作用而备受关注。在本研究中，我们通过大脑中动脉远端闭塞诱导小鼠中风后，静脉注射Muse细胞。在中风诱导2周后，我们评估了运动结果、脾细胞群体、细胞因子谱和基因表达。此外，还对脾切除小鼠和接受过继性脾细胞转移小鼠的结果进行了比较，以了解脾脏对治疗效果的具体影响。我们的研究结果表明，Muse细胞疗法有助于运动恢复，而在没有脾脏的情况下，这种效果会受到影响。接受治疗的小鼠脾脏中性粒细胞计数发生变化，细胞因子活性增加，与蛋白质折叠相关的基因表达显著上升。这些发现证实了Muse细胞在中风后治疗策略中的潜在治疗作用，其疗效至少部分归因于涉及脾脏的免疫调节途径。
