Wright Karina T, El Masri Wagih, Osman Aheed, Roberts Sally, Chamberlain Giselle, Ashton Brian A, Johnson William E B
Centre for Spinal Studies, Robert Jones & Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire SY10 7AG, UK.
Biochem Biophys Res Commun. 2007 Mar 9;354(2):559-66. doi: 10.1016/j.bbrc.2007.01.013. Epub 2007 Jan 10.
In animal models, transplantation of bone marrow stromal cells (MSC) into the spinal cord following injury enhances axonal regeneration and promotes functional recovery. How these improvements come about is currently unclear. We have examined the interaction of MSC with neurons, using an established in vitro model of nerve growth, in the presence of substrate-bound extracellular molecules that are thought to inhibit axonal regeneration, i.e., neural proteoglycans (CSPG), myelin associated glycoprotein (MAG) and Nogo-A. Each of these molecules repelled neurite outgrowth from dorsal root ganglia (DRG) in a concentration-dependent manner. However, these nerve-inhibitory effects were much reduced in MSC/DRG co-cultures. Video microscopy demonstrated that MSC acted as "cellular bridges" and also "towed" neurites over the nerve-inhibitory substrates. Whereas conditioned medium from MSC cultures stimulated DRG neurite outgrowth over type I collagen, it did not promote outgrowth over CSPG, MAG or Nogo-A. These findings suggest that MSC transplantation may promote axonal regeneration both by stimulating nerve growth via secreted factors and also by reducing the nerve-inhibitory effects of the extracellular molecules present.
在动物模型中，损伤后将骨髓基质细胞（MSC）移植到脊髓中可增强轴突再生并促进功能恢复。目前尚不清楚这些改善是如何实现的。我们使用已建立的神经生长体外模型，在存在被认为抑制轴突再生的底物结合细胞外分子（即神经蛋白聚糖（CSPG）、髓磷脂相关糖蛋白（MAG）和Nogo - A）的情况下，研究了MSC与神经元的相互作用。这些分子中的每一种都以浓度依赖的方式排斥背根神经节（DRG）的神经突生长。然而，在MSC/DRG共培养中，这些神经抑制作用大大降低。视频显微镜显示，MSC起到了“细胞桥”的作用，还能在神经抑制底物上“牵引”神经突。虽然MSC培养物的条件培养基刺激DRG神经突在I型胶原上生长，但它并不能促进在CSPG、MAG或Nogo - A上的生长。这些发现表明，MSC移植可能通过分泌因子刺激神经生长以及减少细胞外分子的神经抑制作用来促进轴突再生。
