Mesenchymal stromal-cell transplants induce oligodendrocyte progenitor migration and remyelination in a chronic demyelination model.
Mesenchymal stromal-cell transplants induce oligodendrocyte progenitor migration and remyelination in a chronic demyelination model.
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DOI：
10.1038/cddis.2013.304
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发表时间：
2013-08-29
影响因子：
9
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中科院分区：
文献类型：
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脱髓鞘疾病如脑白质营养不良和多发性硬化是以髓鞘的进行性损失为特征的神经变性疾病，其可导致脑白色物质的慢性脱髓鞘，损害正常轴突传导速度并最终引起神经变性。目前改变病理机制的治疗能够改善疾病;然而，通常，这些治疗不足以将进行性脱髓鞘抑制为慢性病症和永久性功能丧失。为此，我们分析了骨髓间充质干细胞（BM-MSC）移植物在慢性脱髓鞘小鼠脑中发挥的作用。结果，由于移植的MSC表达各种营养信号，移植物周围的少突胶质细胞祖细胞被招募。虽然在非移植侧没有明显的反应，但在移植区域检测到少突胶质细胞祖细胞。这些祖细胞来源于附近的组织以及神经源性龛，包括室管膜下区和齿状回。一旦接近移植部位，细胞成熟为髓鞘少突胶质细胞。最后，电生理研究表明，轴突传导速度显着增加，在移植侧的伞。总之，我们在这里证明，在慢性脱髓鞘的白色物质，骨髓间充质干细胞移植激活少突胶质细胞祖细胞和诱导周围的干细胞移植物的组织髓鞘再生。
Demyelinating disorders such as leukodystrophies and multiple sclerosis are neurodegenerative diseases characterized by the progressive loss of myelin that may lead toward a chronic demyelination of the brain's white matter, impairing normal axonal conduction velocity and ultimately causing neurodegeneration. Current treatments modifying the pathological mechanisms are capable of ameliorating the disease; however, frequently, these therapies are not sufficient to repress the progressive demyelination into a chronic condition and permanent loss of function. To this end, we analyzed the effect that bone marrow-derived mesenchymal stromal cell (BM-MSC) grafts exert in a chronically demyelinated mouse brain. As a result, oligodendrocyte progenitors were recruited surrounding the graft due to the expression of various trophic signals by the grafted MSCs. Although there was no significant reaction in the non-grafted side, in the grafted regions oligodendrocyte progenitors were detected. These progenitors were derived from the nearby tissue as well as from the neurogenic niches, including the subependymal zone and dentate gyrus. Once near the graft site, the cells matured to myelinating oligodendrocytes. Finally, electrophysiological studies demonstrated that axonal conduction velocity was significantly increased in the grafted side of the fimbria. In conclusion, we demonstrate here that in chronic demyelinated white matter, BM-MSC transplantation activates oligodendrocyte progenitors and induces remyelination in the tissue surrounding the stem cell graft.
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影响因子：
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作者：
Chari DM
通讯作者：
Chari DM
影响因子：
3.4
作者：
Boyd, JG;Gordon, T
通讯作者：
Gordon, T
影响因子：
64.8
作者：
BARRES, BA;RAFF, MC;BARDE, YA
通讯作者：
BARDE, YA
影响因子：
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作者：
Hartig, Sean M
通讯作者：
Hartig, Sean M
影响因子：
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作者：
Rivera, Francisco J.;Siebzehnrubl, Florian A.;Aigner, Ludwig
通讯作者：
Aigner, Ludwig