Guiding migration of transplanted glial progenitor cells in the injured spinal cord.
Guiding migration of transplanted glial progenitor cells in the injured spinal cord.
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DOI：
10.1038/srep22576
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发表时间：
2016-03-14
影响因子：
4.6
通讯作者：
Fischer I
中科院分区：
文献类型：
--
作者：
Yuan XB;Jin Y;Haas C;Yao L;Hayakawa K;Wang Y;Wang C;Fischer I
胶质限制性祖细胞（GRP）的移植是一种有前途的策略，为轴突生长在受损的脊髓中产生一个支持性的环境。在这里，我们探讨了通过定向线索产生GRP迁移流以创建轴突再生的支持性通路的可能性。我们发现，轴突生长抑制剂硫酸软骨素蛋白聚糖（CSPG）强烈抑制GRP的粘附和迁移，这种作用可以通过粘附分子层粘连蛋白来调节。具有软骨素酶的CSPG的二羟甲基葡糖胺聚糖侧链改善了GRP在印刷在盖玻片上的CSPG条纹上的迁移，尽管GRP仍然对CSPG的剩余排斥信号有响应。在所有测试的因素中，碱性成纤维细胞生长因子（bFGF）在促进培养的GRP迁移方面具有最显著的效果。当GRP被移植到成年大鼠的正常脊髓或脊髓损伤的背柱半切模型中的损伤部位时，移植细胞的群体向注射有表达软骨素酶或bFGF的慢病毒的区域迁移。这些发现表明，去除CSPG介导的抑制，结合有吸引力的因素的指导，可以是一个有前途的策略，以产生一个迁移流的支持GRP。
Transplantation of glial-restricted progenitors (GRPs) is a promising strategy for generating a supportive environment for axon growth in the injured spinal cord. Here we explored the possibility of producing a migratory stream of GRPs via directional cues to create a supportive pathway for axon regeneration. We found that the axon growth inhibitor chondroitin sulfate proteoglycan (CSPG) strongly inhibited the adhesion and migration of GRPs, an effect that could be modulated by the adhesion molecule laminin. Digesting glycosaminoglycan side chains of CSPG with chondroitinase improved GRP migration on stripes of CSPG printed on cover glass, although GRPs were still responsive to the remaining repulsive signals of CSPG. Of all factors tested, the basic fibroblast growth factor (bFGF) had the most significant effect in promoting the migration of cultured GRPs. When GRPs were transplanted into either normal spinal cord of adult rats or the injury site in a dorsal column hemisection model of spinal cord injury, a population of transplanted cells migrated toward the region that was injected with the lentivirus expressing chondroitinase or bFGF. These findings suggest that removing CSPG-mediated inhibition, in combination with guidance by attractive factors, can be a promising strategy to produce a migratory stream of supportive GRPs.