Bantubungi Kadiombo, Blum David, Cuvelier Laetitia, Wislet-Gendebien Sabine, Rogister Bernard, Brouillet Emmanuel, Schiffmann Serge N
Laboratory of Neurophysiology, ULB-Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium.
Mol Cell Neurosci. 2008 Mar;37(3):454-70. doi: 10.1016/j.mcn.2007.11.001. Epub 2007 Nov 12.
Neural and mesenchymal stem cells have been proposed as alternative sources of cells for transplantation into the brain in neurodegenerative disorders. However, the endogenous factors controlling their engraftment within the injured parenchyma remain ill-defined. Here, we demonstrate significant engraftment of undifferentiated exogenous mesenchymal or neural stem cells throughout the lesioned area in a rat model for Huntington's disease, as late as 8 weeks post-transplantation. We show that stem cell factor (SCF), strongly up-regulated within host cells in the damaged striatum, is able to activate the SCF receptor c-kit and its signaling pathway and to promote the migration and proliferation of mesenchymal and neural stem cells in vitro. Furthermore, c-kit receptor blockade alters neural stem cell distribution within the lesioned striatum. Host SCF expression is observed in atypical cells expressing glial fibrillary acidic protein and doublecortin in the lesioned striatum and in migrating doublecortin-positive progenitors. Taken together, these data demonstrate that SCF produced in situ in the lesioned striatum is an important factor in promoting the engraftment of stem cells within the lesioned brain.
神经干细胞和间充质干细胞已被提议作为神经退行性疾病中移植到大脑的替代性细胞来源。然而，控制它们在受损实质内植入的内源性因素仍不清楚。在此，我们证明在亨廷顿舞蹈病大鼠模型中，未分化的外源性间充质干细胞或神经干细胞在整个损伤区域有显著植入，移植后8周仍可见。我们发现，在受损纹状体的宿主细胞中强烈上调的干细胞因子（SCF）能够激活SCF受体c-kit及其信号通路，并促进间充质干细胞和神经干细胞在体外的迁移和增殖。此外，c-kit受体阻断会改变神经干细胞在受损纹状体内的分布。在受损纹状体中表达胶质纤维酸性蛋白和双皮质素的非典型细胞以及迁移的双皮质素阳性祖细胞中观察到宿主SCF表达。综上所述，这些数据表明，受损纹状体内原位产生的SCF是促进干细胞在受损脑内植入的重要因素。
