Lavdas Alexandros A, Franceschini Isabelle, Dubois-Dalcq Monique, Matsas Rebecca
Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, 127 Vas. Sofias, 11521 Athens, Greece.
Glia. 2006 Jun;53(8):868-78. doi: 10.1002/glia.20340.
Schwann cells, the myelin-forming cells of the PNS, are attractive candidates for remyelination therapy as they can remyelinate CNS axons. Yet their integration in CNS tissue appears hampered, at least in part, by their limited motility in the CNS environment. As the polysialylated (PSA) form of NCAM regulates migration of neural precursors in the CNS and is not expressed by developing Schwann cells, we investigated whether conferring sustained expression of PSA to Schwann cells derived from postnatal rats enhances their motility. Cells were transduced with a retrovirus encoding polysialyl-transferase STX, an enzyme that synthesizes PSA on NCAM. Migration of wild type and transduced cells expressing STX or the marker gene alkaline phosphatase was examined using a gap bridging assay in dissociated cells and by grafting cells in slice cultures of postnatal brain. Migration of PSA expressing cells was significantly increased in both models, as compared to control cells, and this effect was abolished by endoneuraminidase-N stripping of PSA. PSA-positive Schwann cells retained the ability to differentiate in vitro and expressed the Krox20 and P zero myelination markers. When grafted in neonatal cerebellar slices, STX-transduced cells started to myelinate Purkinje cell axons like control cells and make myelin internodes after 2 to 3 weeks. PSA was redistributed on the cell membrane and downregulated during differentiation in pure Schwann cell cultures and slice co-cultures. Thus, migratory properties of PNS myelin-forming cells within the CNS can be enhanced without altering their differentiation program. This finding may be beneficial for the development of remyelination therapies.
雪旺细胞是周围神经系统（PNS）中形成髓鞘的细胞，作为髓鞘再生治疗的候选细胞很有吸引力，因为它们可以使中枢神经系统（CNS）轴突重新髓鞘化。然而，它们在中枢神经系统组织中的整合似乎至少部分受到其在中枢神经系统环境中有限运动能力的阻碍。由于多唾液酸化（PSA）形式的神经细胞黏附分子（NCAM）调节中枢神经系统中神经前体的迁移，且发育中的雪旺细胞不表达该分子，我们研究了赋予新生大鼠来源的雪旺细胞持续表达PSA是否能增强其运动能力。用编码多唾液酸转移酶STX的逆转录病毒转导细胞，STX是一种在NCAM上合成PSA的酶。使用解离细胞中的间隙桥接试验以及通过将细胞移植到新生脑片培养物中，检测表达STX或标记基因碱性磷酸酶的野生型细胞和转导细胞的迁移情况。与对照细胞相比，在两种模型中表达PSA的细胞的迁移均显著增加，并且通过用神经氨酸酶-N去除PSA可消除这种效应。PSA阳性的雪旺细胞保留了体外分化的能力，并表达Krox20和P0髓鞘形成标记物。当移植到新生小脑切片中时，转导STX的细胞开始像对照细胞一样使浦肯野细胞轴突髓鞘化，并在2至3周后形成髓鞘节段。在纯雪旺细胞培养物和切片共培养物中，PSA在细胞膜上重新分布并在分化过程中下调。因此，在不改变其分化程序的情况下，可以增强中枢神经系统内周围神经系统髓鞘形成细胞的迁移特性。这一发现可能对髓鞘再生治疗的发展有益。
