Human Mesenchymal Stem Cells Infiltrate the Spinal Cord, Reduce Demyelination, and Localize to White Matter Lesions in Experimental Autoimmune Encephalomyelitis
Human Mesenchymal Stem Cells Infiltrate the Spinal Cord, Reduce Demyelination, and Localize to White Matter Lesions in Experimental Autoimmune Encephalomyelitis
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DOI：
10.1097/nen.0b013e3181f97392
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发表时间：
2010-11-01
影响因子：
3.2
通讯作者：
Scolding, Neil J.
中科院分区：
文献类型：
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作者：
Gordon, David;Pavlovska, Gordana;Scolding, Neil J.
间充质干细胞(MSCs)可以消除多发性硬化症、实验性自身免疫性脑脊髓炎(EAE)的动物模型，但这种治疗效果是否完全通过全身免疫调节发生，以及中枢神经系统是否在外周分娩后发生浸润尚不确定。我们研究了静脉注射人骨髓间充质干细胞(HMSCs)对C57BL/6小鼠EAE的临床和神经病理学影响。人骨髓间充质干细胞显著降低了临床疾病的严重程度，特别是在晚期疾病。在幼鼠和EAE小鼠中，大量的hMSCs迁移到脊髓各个水平的灰质和白质中。在后者中，hMSCs随着时间的推移在脱髓鞘区域聚集。组织中的hMSCs有两种明显的形态特征，即圆形和数量较少的突起，极少表达神经标志物。HMSC治疗后脊髓白质病变数目和白质脱髓鞘面积均较对照组减少。这些发现表明，中枢神经系统的浸润发生在hMSCs的外周输送后，它们聚集在有髓鞘损伤的地方，并且它们与脱髓鞘程度的减轻有关。这些数据支持hMSCs在多发性硬化症的自体细胞治疗中的潜在作用。
Mesenchymal stem cells (MSCs) can abrogate the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), but whether this therapeutic effect occurs entirely through systemic immune modulation and whether CNS infiltration occurs after peripheral delivery are uncertain. We studied the clinical and neuropathologic effects of intravenously administered human MSCs (hMSCs) in C57BL/6 mice with EAE. Human MSCs significantly reduced the clinical disease severity, particularly in later disease. Large numbers of hMSCs migrated into gray and white matter at all levels of the spinal cord in both naive mice and mice with EAE. In the latter, hMSCs accumulated over time in demyelinated areas. There were 2 distinct morphological appearances of the hMSCs in the tissue, that is, rounded and less numerous process-bearing forms; very few expressed neural markers. The number of spinal cord white matter lesions and areas of white matter demyelination were reduced after hMSC treatment compared with control treatment. These findings show that central nervous system infiltration occurs after peripheral delivery of hMSCs, that they accumulate where there is myelin damage, and that they are associated with a reduced extent of demyelination. These data support a potential role for hMSCs in autologous cell therapy in multiple sclerosis.