Schäfer Richard, Ayturan Miriam, Bantleon Rüdiger, Kehlbach Rainer, Siegel Georg, Pintaske Joerg, Conrad Sabine, Wolburg Hartwig, Northoff Hinnak, Wiskirchen Jakub, Weissert Robert
Institute of Clinical and Experimental Transfusion Medicine, University Hospital Tübingen, Tübingen, Germany.
Cell Transplant. 2008;17(8):923-41. doi: 10.3727/096368908786576480.
Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). Mesenchymal stem cells (MSC) have been shown to ameliorate symptoms in experimental autoimmune encephalomyelitis (EAE), a model of MS. Using cloned MSC labeled with clinically approved small particles of iron oxide (SPIO) for treatment of EAE we analyzed the tissue localization of transferred cells. Treatment with unlabeled MSC led to disease amelioration compared to controls. In contrast, treatment with SPIO-labeled MSC lead to increase in disease severity. Treatment with SPIO alone did not alter disease course. After transplantation labeled and nonlabeled MSC were detected in the CNS and the liver with significantly more SPIO-labeled cells present in the CNS. Iron deposition was present in the group treated with SPIO-labeled MSC, indicating that in vivo the initially cell surface-bound iron detached from the MSC. These results could be of great importance for imaging of patients in the clinical setting, indicating that in vivo application of SPIO-labeled MSC needs to be performed with caution because the cell-derived exposure of iron can lead to disease aggravation.
多发性硬化症(MS)是一种中枢神经系统(CNS)的炎症性脱髓鞘疾病。间充质干细胞(MSC)已被证明可改善实验性自身免疫性脑脊髓炎(EAE,一种MS模型)的症状。我们使用用临床批准的小氧化铁颗粒(SPIO)标记的克隆MSC来治疗EAE,并分析了转移细胞的组织定位。与对照组相比,用未标记的MSC治疗可改善疾病。相反,用SPIO标记的MSC治疗导致疾病严重程度增加。单独用SPIO治疗不会改变疾病进程。移植后,在CNS和肝脏中检测到标记和未标记的MSC,CNS中存在明显更多的SPIO标记细胞。在用SPIO标记的MSC治疗的组中存在铁沉积,这表明在体内最初细胞表面结合的铁从MSC上脱离。这些结果对于临床环境中患者的成像可能非常重要,表明在体内应用SPIO标记的MSC时需要谨慎,因为细胞源性铁暴露可能导致疾病加重。