Adult neural progenitor cells provide a permissive guiding substrate for corticospinal axon growth following spinal cord injury
Adult neural progenitor cells provide a permissive guiding substrate for corticospinal axon growth following spinal cord injury
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DOI：
10.1111/j.1460-9568.2004.03657.x
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发表时间：
2004-10-01
影响因子：
3.4
通讯作者：
Weidner, N
中科院分区：
文献类型：
--
作者：
Pfeifer, K;Vroemen, M;Weidner, N
成体神经前体细胞（NPC）是中枢神经系统（CNS）损伤后细胞移植和神经组织替代的理想来源。将NPC细胞悬液移植到急性损伤的大鼠脊髓中后，NPC存活;然而，它们迁移离开损伤部位并且不能替换损伤诱导的损伤腔。在本研究中，我们检查了（i）NPC与原代成纤维细胞共移植后是否可以保留在病变部位内，以及（ii）NPC是否促进脊髓损伤后的轴突再生。NPC与成纤维细胞共培养证明NPC粘附于成纤维细胞及其产生的细胞外基质。在成纤维细胞的存在下，共培养的NPC的分化模式转向胶质细胞分化。将成年大鼠脊髓来源的NPC与原代成纤维细胞作为混合细胞悬液移植到急性损伤的成年大鼠颈脊髓中3周后，病变腔被完全取代。NPC在整个移植物中存活，并仅分化为胶质细胞。定量的神经元标记的轴突和顺行标记的皮质脊髓轴突表明，NPC与成纤维细胞共移植显着增强轴突再生。神经胶质细胞标记的轴突和皮质脊髓轴突都沿表达GFAP的NPC衍生细胞纵向沿着，其显示出让人联想到未成熟星形胶质细胞的双极形态。因此，移植的星形胶质细胞分化的NPC通过细胞引导促进脊髓损伤后轴突再生。
Adult neural progenitor cells (NPC) are an attractive source for cell transplantation and neural tissue replacement after central nervous system (CNS) injury. Following transplantation of NPC cell suspensions into the acutely injured rat spinal cord, NPC survive; however, they migrate away from the lesion site and are unable to replace the injury-induced lesion cavity. In the present study we examined (i) whether NPC can be retained within the lesion site after co-transplantation with primary fibroblasts, and (ii) whether NPC promote axonal regeneration following spinal cord injury. Co-cultivation of NPC with fibroblasts demonstrated that NPC adhere to fibroblasts and the extracellular matrix produced by fibroblasts. In the presence of fibroblasts, the differentiation pattern of co-cultivated NPC was shifted towards glial differentiation. Three weeks after transplantation of adult spinal-cord-derived NPC with primary fibroblasts as mixed cell suspensions into the acutely injured cervical spinal cord in adult rats, the lesion cavity was completely replaced. NPC survived throughout the graft and differentiated exclusively into glial cells. Quantification of neurofilament-labeled axons and anterogradely labeled corticospinal axons indicated that NPC co-grafted with fibroblasts significantly enhanced axonal regeneration. Both neurofilament-labeled axons and corticospinal axons aligned longitudinally along GFAP-expressing NPC-derived cells, which displayed a bipolar morphology reminiscent of immature astroglia. Thus, grafted astroglial differentiated NPC promote axon regrowth following spinal cord injury by means of cellular guidance.