Department of Physiology, Yonsei University College of Medicine, Seoul, Korea.
Yonsei Med J. 2013 Jan 1;54(1):246-52. doi: 10.3349/ymj.2013.54.1.246.
Cell transplantation of myelin-producing exogenous cells is being extensively explored as a means of remyelinating axons in X-linked adrenoleukodystrophy. We determined whether 3,3',5-Triiodo-L-thyronine (T3) overexpresses the ABCD2 gene in the polysialylated (PSA) form of neural cell adhesion molecule (NCAM)-positive cells and promotes cell proliferation and favors oligodendrocyte lineage differentiation.
PSA-NCAM+ cells from newborn Sprague-Dawley rats were grown for five days on uncoated dishes in defined medium with or without supplementation of basic fibroblast growth factor (bFGF) and/or T3. Then, PSA-NCAM+ spheres were prepared in single cells and transferred to polyornithine/fibronectin-coated glass coverslips for five days to determine the fate of the cells according to the supplementation of these molecules. T3 responsiveness of ABCD2 was analyzed using real-time quantitative polymerase chain reaction, the growth and fate of cells were determined using 5-bromo-2-deoxyuridine incorporation and immunocytochemistry, respectively.
Results demonstrated that T3 induces overexpression of the ABCD2 gene in PSA-NCAM+ cells, and can enhance PSA-NCAM+ cell growth in the presence of bFGF, favoring an oligodendrocyte fate.
These results may provide new insights into investigation of PSA-NCAM+ cells for therapeutic application to X-linked adrenoleukodystrophy.
髓鞘产生的外源性细胞的移植作为一种在 X 连锁肾上腺脑白质营养不良中使轴突重新髓鞘化的方法，正在被广泛研究。我们确定 3,3',5-三碘-L-甲状腺素（T3）是否以多涎酸化（PSA）形式的神经细胞黏附分子（NCAM）阳性细胞过表达 ABCD2 基因，并促进细胞增殖和有利于少突胶质细胞谱系分化。
将新生 Sprague-Dawley 大鼠的 PSA-NCAM+细胞在无涂层培养皿中于限定培养基中培养五天，培养基中添加或不添加碱性成纤维细胞生长因子（bFGF）和/或 T3。然后，将 PSA-NCAM+球体在单细胞中制备，并转移到多聚鸟氨酸/纤维连接蛋白包被的玻璃盖玻片上，根据这些分子的补充情况确定细胞的命运。使用实时定量聚合酶链反应分析 ABCD2 的 T3 反应性，使用 5-溴-2-脱氧尿苷掺入和免疫细胞化学分别确定细胞的生长和命运。
结果表明，T3 诱导 PSA-NCAM+细胞中 ABCD2 基因的过表达，并能在 bFGF 的存在下增强 PSA-NCAM+细胞的生长，有利于少突胶质细胞命运。
这些结果可能为研究用于治疗 X 连锁肾上腺脑白质营养不良的 PSA-NCAM+细胞提供新的见解。
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