Identification of chemoattractive factors involved in the migration of bone marrow-derived mesenchymal stem cells to brain lesions caused by prion
Identification of chemoattractive factors involved in the migration of bone marrow-derived mesenchymal stem cells to brain lesions caused by prion
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骨髓间充质干细胞向朊病毒引起的脑损伤迁移的趋化因子的鉴定
DOI：
10.1128/jvi.05318-11
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发表时间：
2011
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影响因子：
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et al
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作者：
Song;C.H.;et al
据报道，骨髓间充质干细胞（MSC）可迁移至神经退行性疾病的脑部病变；然而，间充质干细胞迁移的确切机制仍有待阐明。在这项研究中，我们进行了体外迁移试验，以研究朊病毒感染小鼠大脑中间充质干细胞的化学吸引因素。使用抗趋化因子受体 CCR3、CCR5、CXCR3 和 CXCR4 的抗体进行预处理，以及使用抗相应配体的抗体预处理感染朊病毒的小鼠脑提取物，可减少永生化人 MSC (hMSC) 的迁移，表明这些受体及其配体参与 hMSC 的迁移。与体外迁移测定的结果一致，被认为从移植区域向朊病毒感染小鼠的脑损伤迁移的胼胝体中的hMSC表达CCR3、CCR5、CXCR3和CXCR4。体外和体内联合分析表明，CCR3、CCR5、CXCR3和CXCR4及其相应的配体参与hMSCs向朊病毒增殖引起的脑损伤的迁移。此外，迁移至朊病毒感染小鼠右侧海马的hMSC表达CCR1、CX3CR1和CXCR4，这意味着这些趋化因子受体参与趋化迁移后的hMSC功能。进一步阐明间充质干细胞迁移的机制可能会为间充质干细胞在朊病毒疾病治疗中的应用提供有用的信息。
Bone marrow-derived mesenchymal stem cells (MSCs) have been reported to migrate to brain lesions of neurodegenerative diseases; however, the precise mechanisms by which MSCs migrate remain to be elucidated. In this study, we carried out anin vitromigration assay to investigate the chemoattractive factors for MSCs in the brains of prion-infected mice. The migration of immortalized human MSCs (hMSCs) was reduced by their pretreatment with antibodies against the chemokine receptors, CCR3, CCR5, CXCR3, and CXCR4 and by pretreatment of brain extracts of prion-infected mice with antibodies against the corresponding ligands, suggesting the involvement of these receptors, and their ligands in the migration of hMSCs. In agreement with the results of anin vitromigration assay, hMSCs in the corpus callosum, which are considered to be migrating from the transplanted area toward brain lesions of prion-infected mice, expressed CCR3, CCR5, CXCR3, and CXCR4. The combinedin vitroandin vivoanalyses suggest that CCR3, CCR5, CXCR3, and CXCR4, and their corresponding ligands are involved in the migration of hMSCs to the brain lesions caused by prion propagation. In addition, hMSCs that had migrated to the right hippocampus of prion-infected mice expressed CCR1, CX3CR1, and CXCR4, implying the involvement of these chemokine receptors in hMSC functions after chemotactic migration. Further elucidation of the mechanisms that underlie the migration of MSCs may provide useful information regarding application of MSCs to the treatment of prion diseases.