Simard Alain R, Rivest Serge
Laboratory of Molecular Endocrinology, CHUL Research Center and Department of Anatomy and Physiology, Laval University, Québec, Canada.
FASEB J. 2004 Jun;18(9):998-1000. doi: 10.1096/fj.04-1517fje. Epub 2004 Apr 14.
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.
多能干细胞在组织发育和再生过程中可分化为多种细胞类型。然而，骨髓来源的干细胞是否能在中枢神经系统（CNS）的许多区域穿过血脑屏障，以及这些细胞是否能轻易分化为功能性实质小胶质细胞，目前仍不清楚。因此，我们研究了骨髓干细胞移入CNS后的分化命运。为此，我们将表达绿色荧光蛋白（GFP）的干细胞系统地移植到接受致死剂量照射的小鼠体内，发现这些细胞移入了CNS多个区域的脑实质。几乎所有浸润细胞都具有高度分支的形态，并与小胶质细胞标志物iba1共定位。此外，这些细胞高水平表达蛋白CD11c，表明骨髓来源的小胶质细胞可能是有效的抗原呈递细胞。这些数据表明，血液来源的小胶质细胞可能激活适应性免疫系统的细胞并对CNS造成损害。因此，这些结果对于免疫源性神经疾病和接受异基因造血干细胞移植的癌症患者可能具有重大的临床意义。
