Aguirre Adan, Rizvi Tilat A, Ratner Nancy, Gallo Vittorio
Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.
J Neurosci. 2005 Nov 30;25(48):11092-106. doi: 10.1523/JNEUROSCI.2981-05.2005.
Approaches to successful cell transplantation therapies for the injured brain involve selecting the appropriate neural progenitor type and optimizing the efficiency of the cell engraftment. Here we show that epidermal growth factor receptor (EGFR) expression enhances postnatal neural progenitor migration in vitro and in vivo. Migratory NG2-expressing (NG2+) progenitor cells of the postnatal subventricular zone (SVZ) express higher EGFR levels than nonmigratory, cortical NG2+ cells. The higher endogenous EGFR expression in SVZ NG2+ cells is causally related with their migratory potential in vitro as well as in vivo after cell engraftment. EGFR overexpression in cortical NG2+ cells by transient transfection converted these cells to a migratory phenotype in vitro and in vivo. Finally, cortical NG2+ cells purified from a transgenic mouse in which the EGFR is overexpressed under the CNP promoter exhibited enhanced migratory capability. These findings reveal a new role for EGFR in the postnatal brain and open new avenues to optimize cell engraftment for brain repair.
成功的脑损伤细胞移植治疗方法包括选择合适的神经祖细胞类型和优化细胞植入效率。我们在此表明,表皮生长因子受体(EGFR)的表达可增强出生后神经祖细胞在体外和体内的迁移。出生后脑室下区(SVZ)表达NG2的迁移性祖细胞(NG2+)比非迁移性的皮质NG2+细胞表达更高水平的EGFR。SVZ NG2+细胞中较高的内源性EGFR表达与其在体外以及细胞植入后的体内迁移潜能存在因果关系。通过瞬时转染在皮质NG2+细胞中过表达EGFR,可使这些细胞在体外和体内转变为迁移表型。最后,从在CNP启动子控制下过表达EGFR的转基因小鼠中纯化得到的皮质NG2+细胞表现出增强的迁移能力。这些发现揭示了EGFR在出生后脑中的新作用,并为优化用于脑修复的细胞植入开辟了新途径。