The astrocyte inhibition of peripheral nerve regeneration is reversed by Schwann cells.
The astrocyte inhibition of peripheral nerve regeneration is reversed by Schwann cells.
复制标题
星形胶质细胞对周围神经再生的抑制被雪旺细胞逆转。
DOI：
10.1006/exnr.1994.1041
复制
发表时间：
1994
影响因子：
5.3
通讯作者：
Bunge,RP
中科院分区：
文献类型：
--
作者：
Guénard,V;Aebischer,P;Bunge,RP
雪旺细胞移植到受损或脱髓鞘的中枢神经系统（CNS）正在被广泛探索作为一种方法，以有利地影响在CNS中的修复。然而，在各种情况下，中枢神经系统神经胶质微环境似乎提供了一个不利的地形促进神经突伸长和雪旺细胞分化。由于损伤部位细胞内容物的异质性，目前尚不清楚每种细胞类型在限制雪旺细胞功能中的具体作用。受损的周围神经系统，一个系统能够大量再生（和少突胶质细胞的潜在负面影响），代表了一个有价值的模型，特别是评估星形胶质细胞对雪旺细胞功能的影响。在本研究中，将纯化的皮质星形胶质细胞群体单独或与成年雪旺细胞群体组合接种到半透性引导通道中，以确定其对成年大鼠横断坐骨神经中8 mm间隙再生的影响。制备具有（或不具有）确定的细胞内容物的通道，植入近交系刘易斯大鼠中并在3周后进行评价。单独接种星形胶质细胞的通道阻碍了再生，无论星形胶质细胞的成熟度（培养7 - 8天vs 28天）和接种密度（40 vs 80 × 106个细胞/ml）如何。另一方面，来自成年坐骨神经的雪旺细胞以相似的密度接种增强了再生过程。当星形胶质细胞与雪旺细胞结合时，再生能力减弱;再生速率随着星形胶质细胞/雪旺细胞混合物中雪旺细胞数量的增加而增加。与星形胶质细胞接种的通道相关的神经残端和星形胶质细胞-雪旺细胞接种的通道中的再生组织的免疫染色表明星形胶质细胞已经迁移到近端神经印记中;仅少数星形胶质细胞保留在再生电缆内。目前的实验表明，虽然星形胶质细胞单独抑制神经再生，许旺细胞能够部分克服这种抑制，如果他们提供了足够的数量。我们相信这些观察将是有价值的，在考虑临床策略，使用自体雪旺细胞移植，以影响中枢神经系统的再生。
Schwann cell transplantation into the lesioned or demyelinated central nervous system (CNS) is being extensively explored as an approach to favorably influencing repair in the CNS. Under a variety of circumstances, however, the CNS glial microenvironment appears to offer an unfavorable terrain for the promotion of neurite elongation and for Schwann cell differentiation. Due to the heterogeneity of the cellular contents at injury sites, the specific role of each cell type present in limiting Schwann cell function is unclear. The damaged peripheral nervous system, a system capable of substantial regeneration (and free of the potentially negative influence of oligodendrocytes), represents a valuable model in which to specifically evaluate the influence of astrocytes on Schwann cell function. In the present study, purified cortical astrocyte populations were seeded into semipermeable guidance channels alone or in combination with adult Schwann cell populations to determine their effects on regeneration across an 8-mm gap in the transected sciatic nerve of the adult rat. Channels were prepared with (or without) a defined cellular content, implanted in inbred Lewis rats and evaluated after 3 weeks. Channels seeded with astrocytes alone impeded regeneration, regardless of the maturity of the astrocytes (7-8 days vs 28 days in culture) and their seeding density (40 vs 80 × 106cells/ml). On the other hand, Schwann cells derived from adult sciatic nerve seeded at similar densities enhanced the regenerative process. Regenerative capacity was diminished when astrocytes were combined with Schwann cells; the rate of regeneration increased as the number of Schwann cells in the astrocyte/Schwann cell mixture increased. Immunostaining of the nerve stumps related to astrocytes -seeded channels and of the regenerated tissue in the astrocyte-Schwann cell-seeded channels indicated that astrocytes had migrated into the proximal nerve stamp; only a few astrocytes remained within the regenerated cable. The present experiments show that although astrocytes alone inhibit nerve regeneration, Schwann cells are able to partially overcome this inhibition if they are provided in sufficient numbers. We believe these observations will be valuable in considering clinical strategies to use autologous Schwann cell transplantation to influence CNS regeneration.