Bone marrow stem cells have the ability to populate the entire central nervous system into fully differentiated parenchymal microglia
Bone marrow stem cells have the ability to populate the entire central nervous system into fully differentiated parenchymal microglia
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DOI：
10.1096/fj.04-1517fje
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发表时间：
2004-04-01
期刊：
影响因子：
4.8
通讯作者：
Rivest, S
中科院分区：
文献类型：
--
作者：
Simard, AR;Rivest, S
多能干细胞可以在组织发育和再生过程中分化成多种细胞类型。然而，目前尚不清楚骨髓来源的干细胞是否能够跨越中枢神经系统（CNS）许多区域的血脑屏障，以及这些细胞是否能够容易地分化为功能性实质小胶质细胞。因此，我们研究了骨髓干细胞迁移到中枢神经系统后的分化命运。为此，我们系统地将表达绿色荧光蛋白（GFP）的干细胞移植到致死照射的小鼠体内，发现这些细胞迁移到中枢神经系统许多区域的脑实质中。几乎所有浸润细胞都具有高度分叉的形态，并与小胶质标记物iba1共定位。此外，这些细胞表达高水平的CD11c蛋白，表明骨髓来源的小胶质细胞可能是有效的抗原提呈细胞。这些数据表明，血液来源的小胶质细胞可以激活适应性免疫系统的细胞并对中枢神经系统造成伤害。因此，这些结果可能对免疫源性神经疾病和接受同种异体造血干细胞移植的癌症患者具有重要的临床意义。
Pluripotent stem cells can differentiate into a variety of cell types during tissue development and regeneration. However, it is still unclear whether bone marrow-derived stem cells can migrate across the blood-brain barrier in many regions of the central nervous system (CNS) and if these cells can readily differentiate into functional parenchymal microglia. We thus studied the differentiation fate of bone marrow stem cells upon immigration into the CNS. To this end, we systemically transplanted stem cells that express green fluorescent protein (GFP) into lethally irradiated mice and found that these cells immigrated into the brain parenchyma of many regions of the CNS. Nearly all of the infiltrating cells had a highly ramified morphology and colocalized with the microglial marker iba1. Moreover, these cells expressed high levels of the protein CD11c, indicating that microglia of bone marrow origin may be potent antigen presenting cells. These data suggest that microglia of blood origin could activate cells of the adaptive immune system and cause harm to the CNS. Therefore, these results may have great clinical relevance for both immune-derived neuronal disorders and cancer patients undergoing allogeneic hematopoietic stem-cell transplantation.