Naive BM-derived stem cells (Neuro-Cells) may modify acute and chronic neurodegenerative disorders by modulating macrophage behaviors

E. Wolters, T. Strekalova, J. P. Munter, B. Kramer
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引用次数: 3

Abstract

Naive BM-derived stem cells (Neuro-Cells) may modify acute and chronic neurodegenerative disorders by modulating macrophage behaviors. Ageing Neur Abstract In acute traumatic or hypoxic brain and spinal cord lesions, as well as in chronic idiopathic neurodegenerative disorders induced by a genetic/environmental/idiopathic protein misfolding with aggregation, emerging evidence indicates that primary necrosis, as induced by the underlying event, initiates a secondary inflammatory process. In this secondary process, responsible for significant neurological deterioration, a microglia type M1/M2 misbalance plays a major role. Indeed, both acute and chronic neurodegenerative disorders share a common pathway: a M1/M2 misbalance-induced hyperinflammatory process with a lack of response to conventional anti-inflammatory interventions. In recent literature, however, both in preclinical and clinical neurodegenerative conditions, these processes were suggested to be sensitive for interventions with stem cells. Intrathecal interventions with a fresh, not-manipulated (naïve) bone marrow-derived stem cell preparation, after positive selection of pro-inflammatory substances (Neuro-Cells), were found to prevent/reduce secondary necrosis-induced pro-inflammatory and pro-apoptotic processes in both immune-compromised and otherwise healthy experimental animal models. Therefore, it seems justified to further encourage clinical trials applying autologous BM-derived naïve stem cells in patients suffering from those debilitating neurodegenerative conditions.
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原始脑源性干细胞(神经细胞)可能通过调节巨噬细胞的行为来改变急性和慢性神经退行性疾病
原始脑源性干细胞(神经细胞)可能通过调节巨噬细胞的行为来改变急性和慢性神经退行性疾病。在急性创伤性或缺氧性脑和脊髓病变中,以及由遗传/环境/特发性蛋白质错误折叠与聚集引起的慢性特发性神经退行性疾病中,新出现的证据表明,由潜在事件诱导的原发性坏死启动继发性炎症过程。在这一次要过程中,小胶质细胞类型M1/M2失衡起主要作用,导致显著的神经功能恶化。事实上,急性和慢性神经退行性疾病都有一个共同的途径:M1/M2失衡引起的高炎症过程,对传统的抗炎干预缺乏反应。然而,在最近的文献中,在临床前和临床神经退行性疾病中,这些过程被认为对干细胞干预是敏感的。研究发现,在免疫受损和其他健康的实验动物模型中,在阳性选择促炎物质(神经细胞)后,用新鲜的、未经处理的(naïve)骨髓源性干细胞制备鞘内干预可以预防/减少继发性坏死诱导的促炎和促凋亡过程。因此,似乎有理由进一步鼓励临床试验,将自体脑脊髓瘤来源的naïve干细胞应用于患有这些衰弱性神经退行性疾病的患者。
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