Busch Christian, Oppitz Matthias, Sailer Martin H, Just Lothar, Metzger Marco, Drews Ulrich
Anatomisches Institut, Oesterbergstr. 3, D-72074 Tübingen, Germany.
J Cell Sci. 2006 Nov 1;119(Pt 21):4467-74. doi: 10.1242/jcs.03205. Epub 2006 Oct 10.
Central nervous system (CNS) stem cells isolated from the subventricular zone (SVZ) show a remarkable differentiation potential into neural derivatives. Surprisingly adult SVZ cells can also be induced in vitro to differentiate into neural crest cell fates. This fate switch is dependent on the combination of fibroblast growth factor 2 (FGF2) and bone morphogenetic proteins (BMPs). Here we transplanted adult SVZ stem cells from GFP mice as neurospheres into the trunk neural tube of chick and quail embryos. Only neurospheres pre-exposed to BMP-2 and FGF2 formed close contacts with the dorsal neuroepithelium corresponding to the neural crest area. GFP-positive cells emigrated from the neurosphere and were identified in the roof plate, the dorsal neuroepithelium and among emigrating neural crest cells adjacent to the neural tube. Neurospheres not treated with BMP-2 did not integrate into the neuroepithelium. Our data demonstrate that adult CNS stem cells can be efficiently prepared in vitro for integration into the embryonic neural crest. BMP-2 treatment conveys the necessary morphogenetic capabilities to adult stem cells for future clinical transplantation strategies.
从脑室下区（SVZ）分离出的中枢神经系统（CNS）干细胞表现出向神经衍生物分化的显著潜力。令人惊讶的是，成年SVZ细胞在体外也可被诱导分化为神经嵴细胞命运。这种命运转变取决于成纤维细胞生长因子2（FGF2）和骨形态发生蛋白（BMPs）的组合。在此，我们将来自绿色荧光蛋白（GFP）小鼠的成年SVZ干细胞作为神经球移植到鸡和鹌鹑胚胎的躯干神经管中。只有预先暴露于BMP - 2和FGF2的神经球与对应于神经嵴区域的背侧神经上皮形成紧密接触。GFP阳性细胞从神经球中移出，并在顶板、背侧神经上皮以及神经管相邻的移出神经嵴细胞中被鉴定出来。未用BMP - 2处理的神经球未整合到神经上皮中。我们的数据表明，成年CNS干细胞可在体外有效制备以整合到胚胎神经嵴中。BMP - 2处理为成年干细胞赋予了必要的形态发生能力，以用于未来的临床移植策略。
