Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain
Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain
复制标题
DOI：
10.1038/nm974
复制
发表时间：
2004-01-01
期刊：
影响因子：
82.9
通讯作者：
Goldman, SA
中科院分区：
文献类型：
--
作者：
Windrem, MS;Nunes, MC;Goldman, SA
妊娠晚期和成人前脑均含有大量少突胶质前体细胞(OPC)。这些细胞可以通过其A2B5(+)PSA-NCAM(-)表型(早期少突胶质细胞标志物A2B5阳性，多唾液酸神经细胞黏附分子阴性)来鉴定。我们采用双色荧光激活细胞分选法(FACS)从21~23周龄的人胎儿前脑提取OPC，并用A2B5选择从成人脑白质中提取这些细胞。当异种移植到新生寒战小鼠的前脑时，胎儿OPC分散在整个白质中，并发育成少突胶质细胞和星形胶质细胞。12周时，宿主大脑出现广泛的髓鞘生成、致密和轴突髓鞘形成。来自成人白质的OPC分离株也使小鼠脑髓鞘颤抖，但比它们的胎儿同种细胞快得多，在移植后4周实现了广泛和密集的髓鞘碱性蛋白(MBP)的表达。成人OPC比胎儿OPC更有效地生成少突胶质细胞，并且每个供体细胞比胎儿细胞包裹更多的宿主轴突。胎儿和成人的OPC表型都介导了先天性髓鞘异常宿主脑广泛而强大的髓鞘形成，尽管它们的差异表明它们用于不同的疾病靶点。
Both late-gestation and adult human forebrain both contain large numbers of oligodendrocyte progenitor cells (OPCs). These cells may be identified by their A2B5(+)PSA-NCAM(-) phenotype (positive for the early oligodendrocyte marker A2B5 and negative for the polysialylated neural cell adhesion molecule). We used dual-color fluorescence-activated cell sorting (FACS) to extract OPCs from 21- to 23-week-old fetal human forebrain, and A2B5 selection to extract these cells from adult white matter. When xenografted to the forebrains of newborn shiverer mice, fetal OPCs dispersed throughout the white matter and developed into oligodendrocytes and astrocytes. By 12 weeks, the host brains showed extensive myelin production, compaction and axonal myelination. Isolates of OPCs derived from adult human white matter also myelinated shiverer mouse brain, but much more rapidly than their fetal counterparts, achieving widespread and dense myelin basic protein (MBP) expression by 4 weeks after grafting. Adult OPCs generated oligodendrocytes more efficiently than fetal OPCs, and ensheathed more host axons per donor cell than fetal cells. Both fetal and adult OPCS phenotypes mediated the extensive and robust myelination of congenitally dysmyelinated host brain, although their differences suggested their use for different disease targets.