Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Otsu, Japan; Department of Neurosurgery, Shiga University of Medical Science, Otsu, Japan.
Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Otsu, Japan.
Cytotherapy. 2023 Nov;25(11):1186-1199. doi: 10.1016/j.jcyt.2023.07.003. Epub 2023 Aug 8.
Stroke is a frequently observed neurological disorder that might lead to permanent and severe disability. Recently, various regenerative therapies have been developed, some of which have already been applied clinically. However, their outcomes have not been fully satisfactory. In particular, the development of regenerative therapies for chronic ischemic stroke is greatly needed. Herein intracerebral administration of bone marrow-derived mononuclear cells (BM-MNCs) was assessed as a potential treatment for chronic ischemic stroke using a severe combined immunodeficiency mouse model characterized by minimal vascular variation unrelated to immunodeficiency.
A reproducible model of permanent middle cerebral artery occlusion was prepared, and intracerebral BM-MNC transplantation was performed 14 days after stroke induction in the infarcted brain.
Sensorimotor behavioral function and cerebral blood flow were significantly improved upon treatment with BM-MNCs compared to control medium injection. The transplanted cells exhibited characteristics of the vascular endothelium and microglia/macrophages. Significant angiogenesis and suppression of astrogliosis and microgliosis were observed in the affected brain. Messenger RNA expression analysis showed significant increases in anti-inflammatory cytokines, A2 astrocyte/anti-inflammatory microglia markers and vascular endothelial markers such as vascular endothelial growth factor and significant decreases in pro-inflammatory cytokines and A1 astrocyte/pro-inflammatory microglia markers following BM-MNC transplantation.
These results suggest that intracerebral administration of BM-MNCs should be considered an effective cell therapy for chronic stroke.
中风是一种常见的神经系统疾病，可能导致永久性和严重的残疾。最近，已经开发出了各种再生疗法，其中一些已经在临床上应用。然而，它们的效果并不完全令人满意。特别是，需要开发针对慢性缺血性中风的再生疗法。在此，使用一种严重联合免疫缺陷小鼠模型，评估了脑内骨髓来源的单核细胞（BM-MNCs）作为慢性缺血性中风潜在治疗方法的作用，该模型的血管变化与免疫缺陷无关。
制备永久性大脑中动脉闭塞的可重复模型，并在中风诱导后 14 天在梗死大脑中进行脑内 BM-MNC 移植。
与对照培养基注射相比，BM-MNC 治疗可显著改善感觉运动行为功能和脑血流。移植的细胞表现出血管内皮细胞和小胶质细胞/巨噬细胞的特征。在受影响的大脑中观察到明显的血管生成以及星形胶质细胞和小胶质细胞的增生减少。信使 RNA 表达分析显示，BM-MNC 移植后抗炎细胞因子、A2 星形胶质细胞/抗炎小胶质细胞标志物和血管内皮标志物（如血管内皮生长因子）的表达显著增加，促炎细胞因子和 A1 星形胶质细胞/促炎小胶质细胞标志物的表达显著减少。
这些结果表明，脑内给予 BM-MNCs 应被视为慢性中风的有效细胞治疗方法。
