Sadanandan Nadia, Lee Jea-Young, Garbuzova-Davis Svitlana
Georgetown University, Washington, DC, USA.
Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Brain Circ. 2021 Mar 30;7(1):23-28. doi: 10.4103/bc.bc_9_21. eCollection 2021 Jan-Mar.
Amyotrophic lateral sclerosis (ALS) stands as a neurodegenerative disorder characterized by the rapid progression of motor neuron loss in the brain and spinal cord. Unfortunately, treatment options for ALS are limited, and therefore, novel therapies that prevent further motor neuron degeneration are of dire need. In ALS, the infiltration of pathological elements from the blood to the central nervous system (CNS) compartment that spur motor neuron damage may be prevented via restoration of the impaired blood-CNS-barrier. Transplantation of human bone marrow endothelial progenitor cells (hBM-EPCs) demonstrated therapeutic promise in a mouse model of ALS due to their capacity to mitigate the altered blood-CNS-barrier by restoring endothelial cell (EC) integrity. Remarkably, the hBM-EPCs can release angiogenic factors that endogenously ameliorate impaired ECs. In addition, these cells may produce extracellular vesicles (EVs) that carry a wide range of vesicular factors, which aid in alleviating EC damage. In an study, hBM-EPC-derived EVs were effectively uptaken by the mouse brain endothelial cells (mBECs) and cell damage was significantly attenuated. Interestingly, the incorporation of EVs into mBECs was inhibited via β1 integrin hindrance. This review explores preclinical studies of the therapeutic potential of hBM-EPCs, specifically via hBM-EPC-derived EVs, for the repair of the damaged blood-CNS-barrier in ALS as a novel treatment approach.
肌萎缩侧索硬化症（ALS）是一种神经退行性疾病，其特征是大脑和脊髓中的运动神经元迅速丧失。不幸的是，ALS的治疗选择有限，因此，迫切需要能够防止运动神经元进一步退化的新疗法。在ALS中，通过恢复受损的血脑屏障，可以防止病理因素从血液渗入中枢神经系统（CNS）从而刺激运动神经元损伤。人骨髓内皮祖细胞（hBM-EPCs）的移植在ALS小鼠模型中显示出治疗前景，因为它们能够通过恢复内皮细胞（EC）的完整性来减轻改变的血脑屏障。值得注意的是，hBM-EPCs可以释放血管生成因子，内源性改善受损的内皮细胞。此外，这些细胞可能产生携带多种囊泡因子的细胞外囊泡（EVs），有助于减轻内皮细胞损伤。在一项研究中，hBM-EPC衍生的EVs被小鼠脑内皮细胞（mBECs）有效摄取，细胞损伤明显减轻。有趣的是，通过β1整合素阻碍可抑制EVs进入mBECs。本综述探讨了hBM-EPCs治疗潜力的临床前研究，特别是通过hBM-EPC衍生的EVs，作为一种新的治疗方法修复ALS中受损的血脑屏障。
