O'Leary M T, Blakemore W F
MRC Cambridge Centre for Brain Repair, United Kingdom.
J Neurosci Res. 1997 Apr 15;48(2):159-67.
Cell cultures enriched for oligodendrocyte precursors were prepared for male neonatal rat pups and transplanted into the spinal cord white matter of normal and x-irradiated syngeneic adult female rats. Transplanted cells were detected using a probe specific for the rat Y chromosome immediately after transplantation and 14 days later. In non-x-irradiated tissue, significantly fewer cells were seen at 14 days compared with time zero, and no cell migration was observed. In x-irradiated tissue, cells both survived and migrated into the surrounding grey and white matter. The observed behaviour of oligodendrocyte precursors in normal adult tissue is in contrast to their behaviour in myelin mutants and neonates, where migration and survival have been well documented (Warrington et al., 1993; Lachapelle et al., 1994), but mimics the behaviour of the O-2A progenitor-like cell line, CG4, following transplantation into similar environments (Franklin et al., 1996). The findings in this study have profound implications for the use of grafts of oligodendrocyte precursors as a therapy in human demyelinating diseases, because they indicate that grafts will need to be introduced directly into each clinically relevant area of demyelination.
为雄性新生大鼠幼崽制备富含少突胶质细胞前体的细胞培养物,并将其移植到正常和经X射线照射的同基因成年雌性大鼠的脊髓白质中。移植后立即以及14天后,使用针对大鼠Y染色体的探针检测移植细胞。在未接受X射线照射的组织中,与移植后即刻相比,14天时观察到的细胞明显减少,且未观察到细胞迁移。在接受X射线照射的组织中,细胞既能存活,又能迁移到周围的灰质和白质中。少突胶质细胞前体在正常成年组织中的行为与它们在髓磷脂突变体和新生动物中的行为形成对比,在髓磷脂突变体和新生动物中,迁移和存活已有充分记录(沃林顿等人,1993年;拉沙佩勒等人,1994年),但类似于O-2A祖细胞样细胞系CG4在移植到类似环境后的行为(富兰克林等人,1996年)。本研究结果对将少突胶质细胞前体移植作为人类脱髓鞘疾病的一种治疗方法具有深远意义,因为这表明需要将移植物直接引入每个临床相关的脱髓鞘区域。