Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in chronic EAE mice
Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in chronic EAE mice
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DOI：
10.1002/mrm.21116
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Bulte, Jeff W. M.
中科院分区：
文献类型：
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作者：
Ben-Hur, Tamir;van Heeswijk, Ruud B.;Bulte, Jeff W. M.
神经干细胞（NSC）移植已被证明可以减轻实验性自身免疫性脑脊髓炎（EAE）的严重程度，EAE是多发性硬化症（MS）的动物模型。NSC移植在MS中未来成功的关键是移植细胞从移植部位迁移到相关疾病病灶的能力。使用磁标记的小鼠神经球和人胚胎干细胞（hESC）衍生的神经球，我们应用系列磁共振成像（MRI），以评估移植细胞迁移的生物动力学在慢性小鼠EAE模型。磁标记并没有影响在体外和体内的特性的细胞作为多潜能前体。细胞迁移发生在沿着白色物质（WM）束（尤其是胼胝体（CC）、海马伞和内囊），主要发生在疾病急性期的早期，并且以不对称的方式发生。细胞迁移的距离与疾病的临床严重程度和WM束中小胶质细胞的数量密切相关，支持炎症信号促进移植细胞迁移的观点。这项研究首次表明，hESC衍生的神经前体也对MS模型中的组织信号做出反应，类似于啮齿动物细胞。这些结果与设计和优化MS的细胞疗法直接相关，并更好地了解体内细胞动力学和细胞-组织相互作用。
Neural stem cell (NSC) transplantation has been shown to attenuate the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Central to the future success of NSC transplantation in MS is the ability of transplanted cells to migrate from the site of transplantation to relevant foci of disease. Using magnetically labeled mouse neurospheres and human embryonic stem cell (hESC)-derived neurospheres, we applied serial magnetic resonance imaging (MRI) to assess the biodynamics of transplanted cell migration in a chronic mouse EAE model. Magnetic labeling did not affect the in vitro and in vivo characteristics of cells as multipotential precursors. Cell migration occurred along white matter (WM) tracts (especially the corpus callosum (CC), fimbria, and internal capsule), predominantly early in the acute phase of disease, and in an asymmetric manner. The distance of cell migration correlated well with clinical severity of disease and the number of microglia in the WM tracts, supporting the notion that inflammatory signals promote transplanted cell migration. This study shows for the first time that hESC-derived neural precursors also respond to tissue signals in an MS model, similarly to rodent cells. The results are directly relevant for designing and optimizing cell therapies for MS, and achieving a better understanding of in vivo cell dynamics and cell-tissue interactions.