CD44 is required for the migration of transplanted oligodendrocyte progenitor cells to focal inflammatory demyelinating lesions in the spinal cord
CD44 is required for the migration of transplanted oligodendrocyte progenitor cells to focal inflammatory demyelinating lesions in the spinal cord
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DOI：
10.1002/glia.22438
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发表时间：
2013-03-01
期刊：
影响因子：
6.2
通讯作者：
Duncan, Ian D.
中科院分区：
文献类型：
--
作者：
Piao, Jing-Hua;Wang, Yanping;Duncan, Ian D.
多发性硬化症 (MS) 中慢性脱髓鞘轴突的髓鞘再生需要招募内源性细胞或用移植的外源性少突胶质细胞祖细胞 (OPC) 替代。我们之前已经表明，OPC 系 CG4 在移植后优先迁移到大鼠脊髓中注射酵母聚糖造成的炎症脱髓鞘和轴突损失的局部区域。在这里，我们发现许多移植的 CG4 细胞在 1 天后就已经迁移到炎症病变中。我们证明大量已迁移的 CG4 细胞表达粘附蛋白 CD44，并且 CD44 的主要配体透明质酸 (HA) 在炎症病变中强烈表达。在体外迁移测定中，阻断 CG4 细胞上的 CD44 表达后，迁移显着下降。同样，当移植细胞在移植前暴露于 CD44 阻断抗体时，CG4 细胞向体内酵母聚糖损伤的迁移受到抑制。这些发现表明，CD44 是 OPC 向酵母聚糖诱导的局灶性炎症性脱髓鞘病变迁移的关键分子，并且可能在 MS 的 OPC 修复中发挥重要作用。 (C) 2012 年 Wiley 期刊公司。
Remyelination of chronically demyelinated axons in multiple sclerosis (MS) requires the recruitment of endogenous cells or their replacement by transplanted, exogenous oligodendrocyte progenitor cells (OPCs). We have previously shown that an OPC line, CG4, preferentially migrates after transplantation toward focal areas of inflammatory demyelination and axon loss created by injection of zymosan in the rat spinal cord. Here we show that many transplanted CG4 cells had already migrated into the inflammatory lesion after 1 day. We demonstrate that a large number of CG4 cells that had migrated, expressed the adhesion protein, CD44, and that CD44's main ligand, hyaluronic acid (HA) was robustly expressed in the inflammatory lesion. In an in vitro migration assay, migration declined significantly following blocking of CD44 expression on CG4 cells. Likewise, migration of CG4 cells toward a zymosan lesion in vivo was inhibited when transplanted cells were exposed to a CD44 blocking antibody prior to transplantation. These findings suggest that CD44 is a key molecule in the migration of OPCs toward the focal inflammatory demyelinated lesion induced by zymosan, and may be an important in OPC repair in MS. (C) 2012 Wiley Periodicals, Inc.