Polysialylated neural cell adhesion molecule-positive CNS precursors generate both oligodendrocytes and schwann cells to remyelinate the CNS after transplantation
Polysialylated neural cell adhesion molecule-positive CNS precursors generate both oligodendrocytes and schwann cells to remyelinate the CNS after transplantation
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DOI：
10.1523/jneurosci.19-17-07529.1999
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发表时间：
1999-09-01
影响因子：
5.3
通讯作者：
Blakemore, WF
中科院分区：
文献类型：
--
作者：
Keirstead, HS;Ben-Hur, T;Blakemore, WF
移植提供了一种鉴定早期神经前体的分化和髓鞘形成潜力的方法，这些特征与脱髓鞘疾病中的髓鞘再生有关。在出生后的大鼠脑中，表达神经细胞粘附分子NCAM的聚唾液酸化（PSA）形式的前体细胞已显示在体外主要产生少突胶质细胞和星形胶质细胞（Ben-Hur等人，1998年）。免疫选择的PSA-NCAM+新生大鼠CNS前体用FGF 2扩增成簇，并移植到成年大鼠脊髓中的局灶性脱髓鞘病变中。我们发现，这些神经前体细胞可以完全髓鞘这样的中枢神经系统病变。虽然PSA-NCAM+前体簇含有罕见的P75+推定的神经嵴前体，但即使在胶质生长因子存在下，它们也不会在体外产生许旺细胞。然而，当它们在无胶质细胞的区域中遇到脱髓鞘的轴突时，它们在体内产生少突胶质细胞、星形胶质细胞和雪旺细胞。我们证实了这些雪旺细胞的移植起源，使用Y染色体原位杂交和外周髓磷脂蛋白P0的组织从雌性大鼠，已与男性细胞簇移植的免疫染色。有髓鞘组织中许旺细胞的数量和分布，以及供体细胞中P0 mRNA的缺乏，表明许旺细胞是通过移植的PSA-NCAM+神经前体细胞的扩增和分化产生的，而不是来源于污染的许旺细胞。因此，移植到脱髓鞘的CNS组织中揭示了神经前体的意想不到的分化潜力，导致CNS轴突通过PNS和CNS髓鞘形成细胞的髓鞘再生。
Transplantation offers a means of identifying the differentiation and myelination potential of early neural precursors, features relevant to myelin regeneration in demyelinating diseases. In the postnatal rat brain, precursor cells expressing the polysialylated (PSA) form of the neural cell adhesion molecule NCAM have been shown to generate mostly oligodendrocytes and astrocytes in vitro (Ben-Hur et al., 1998). Immunoselected PSA-NCAM+ newborn rat CNS precursors were expanded as clusters with FGF2 and grafted into a focal demyelinating lesion in adult rat spinal cord. We show that these neural precursors can completely remyelinate such CNS lesions. While PSA-NCAM+ precursor clusters contain rare P75+ putative neural crest precursors, they do not generate Schwann cells in vitro even in the presence of glial growth factor. Yet they generate oligodendrocytes, astrocytes, and Schwann cells in vivo when confronted with demyelinated axons in a glia-free area. We confirmed the transplant origin of these Schwann cells using Y chromosome in situ hybridization and immunostaining for the peripheral myelin protein P0 of tissue from female rats that had been grafted with male cell clusters. The number and distribution of Schwann cells within remyelinated tissue, and the absence of P0 mRNAs in donor cells, indicated that Schwann cells were generated by expansion and differentiation of transplanted PSA-NCAM+ neural precursors and were not derived from contaminating Schwann cells. Thus, transplantation into demyelinated CNS tissue reveals an unexpected differentiation potential of a neural precursor, resulting in remyelination of CNS axons by PNS and CNS myelin-forming cells.