Brundin Lou, Brismar Hjalmar, Danilov Alexandre I, Olsson Tomas, Johansson Clas B
Neuroimmunology Unit, Centre of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Brain Pathol. 2003 Jul;13(3):322-8. doi: 10.1111/j.1750-3639.2003.tb00031.x.
In multiple sclerosis, the central nervous system is lesioned through invasion of plaque-forming inflammatory cells, primarily contributing to immune attack of myelin and oligodendrocytes. In this report we address the possible activation and differentiation of central nervous system stem cells following such immunological insults in a well-characterized rat model of multiple sclerosis characterised by spinal cord pathology. Dye-labeled central nervous system stem cells, residing within the ependymal layer of the central canal responded to the multiple sclerosis-like conditions by proliferation, while some of the migrating stem cell-derived cells expressed markers typical for oligodendrocytes (04) and astrocytes (glial fibrillary acidic protein, GFAP) in the demyelinated area. Our results indicate that regenerative stem cell activation following immunoactivity is different from that after trauma, exemplified by the slower time course of stem cell proliferation and migration of progeny, in addition to the ability of the stem cell-derived cells to express oligodendrocyte markers. Finally, deleterious effects of macrophages on the stem cell population were evident and may contribute to the depletion of the stem cell population in neuroinflammatory disorders.
在多发性硬化症中,中枢神经系统因形成斑块的炎性细胞侵入而受损,这主要导致对髓鞘和少突胶质细胞的免疫攻击。在本报告中,我们在一个以脊髓病理为特征的、充分表征的多发性硬化症大鼠模型中,探讨了在这种免疫损伤后中枢神经系统干细胞可能的激活和分化情况。位于中央管室管膜层的染料标记中枢神经系统干细胞对类似多发性硬化症的情况作出增殖反应,而一些迁移的干细胞衍生细胞在脱髓鞘区域表达少突胶质细胞(04)和星形胶质细胞(胶质纤维酸性蛋白,GFAP)的典型标志物。我们的结果表明,免疫活性后的再生干细胞激活与创伤后的不同,其例证为干细胞增殖和子代细胞迁移的时间进程较慢,以及干细胞衍生细胞表达少突胶质细胞标志物的能力。最后,巨噬细胞对干细胞群体的有害作用明显,可能导致神经炎症性疾病中干细胞群体的消耗。