From bone marrow to brain: stem cells in neuroprotection, plasticity, and neuroregeneration

M. Penkowa
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引用次数: 1

Abstract

At present, curative therapies for neurological diseases are limited, even though they are prevalent worldwide. So far, molecular strategies developed for brain disorders act through one single molecular mechanism, yet, these diseases are multifactorial and highly complex, as to why a successful therapy likely calls for a more multifaceted and cell-based approach. The bone marrow contains a mixed stem and progenitor cell population including hematopoietic stem cells (HSC) and mesenchymal stromal stem cells (MSC), which are potential endogenous candidates for cell-based therapy in various brain disorders like stroke, trauma, and neurodegeneration. Unlike the neural stem cells (NSC), bone marrow HSC are readily isolated, mobilized and expanded by means of treatment with granulocyte-colony stimulating factor (G-CSF) and CXCR4-antagonist plerixafor. Once in the blood circulation, the cells preferentially home to injured tissues including the brain. Bone marrow cells may convey neuroprotection, plasticity, and neuroregeneration by different mechanisms of action, which include either transdifferentiation or cell-cell fusion with resident brain cells. Bone marrow cells also benefit the injured brain by secreting bioactive factors, which in a paracrine manner convey intrinsic repair and enhance neurogenesis. Furthermore, transplanted MSC may activate the astrocytes leading to increased glial secretion of neurotrophic growth factors and enhanced proliferation and migration of the resident NSC. These neuroregenerative mechanisms of action are not mutually exclusive, in fact they may provide a multifaceted therapeutic approach, which is requested in order to move neurorestorative and protective strategies into the clinic. Biomedical Reviews 2011; 22: 1-6.
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从骨髓到大脑:干细胞在神经保护、可塑性和神经再生中的作用
目前,神经系统疾病的治疗方法是有限的,尽管它们在世界范围内很普遍。到目前为止,针对大脑疾病开发的分子策略通过单一的分子机制起作用,然而,这些疾病是多因素和高度复杂的,这就是为什么成功的治疗可能需要更多方面和基于细胞的方法。骨髓包含混合的干细胞和祖细胞群,包括造血干细胞(HSC)和间充质基质干细胞(MSC),它们是潜在的内源性候选细胞,用于各种脑部疾病,如中风、创伤和神经变性。与神经干细胞(NSC)不同,骨髓HSC很容易通过粒细胞集落刺激因子(G-CSF)和cxcr4拮抗剂plerixafor进行分离、动员和扩增。一旦进入血液循环,这些细胞就会优先回到受伤的组织,包括大脑。骨髓细胞可能通过不同的作用机制来传递神经保护、可塑性和神经再生,这些机制包括转分化或与常驻脑细胞的细胞-细胞融合。骨髓细胞还通过分泌生物活性因子使受损的大脑受益,这些生物活性因子以旁分泌的方式传递内在修复并促进神经发生。此外,移植的间充质干细胞可能激活星形胶质细胞,导致神经营养生长因子的胶质分泌增加,并增强常驻NSC的增殖和迁移。这些神经再生机制的作用并不是相互排斥的,事实上,它们可能提供多方面的治疗方法,这是为了将神经修复和保护策略带入临床所需要的。生物医学评论2011;22: 1 - 6。
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