StemCells Inc., Newark, CA 94560, USA.
Sci Transl Med. 2012 Oct 10;4(155):155ra136. doi: 10.1126/scitranslmed.3004371.
Shiverer-immunodeficient (Shi-id) mice demonstrate defective myelination in the central nervous system (CNS) and significant ataxia by 2 to 3 weeks of life. Expanded, banked human neural stem cells (HuCNS-SCs) were transplanted into three sites in the brains of neonatal or juvenile Shi-id mice, which were asymptomatic or showed advanced hypomyelination, respectively. In both groups of mice, HuCNS-SCs engrafted and underwent preferential differentiation into oligodendrocytes. These oligodendrocytes generated compact myelin with normalized nodal organization, ultrastructure, and axon conduction velocities. Myelination was equivalent in neonatal and juvenile mice by quantitative histopathology and high-field ex vivo magnetic resonance imaging, which, through fractional anisotropy, revealed CNS myelination 5 to 7 weeks after HuCNS-SC transplantation. Transplanted HuCNS-SCs generated functional myelin in the CNS, even in animals with severe symptomatic hypomyelination, suggesting that this strategy may be useful for treating dysmyelinating diseases.
颤抖易位免疫缺陷（Shi-id）小鼠在中枢神经系统（CNS）中表现出髓鞘形成缺陷，并在生命的 2 至 3 周时出现明显的共济失调。扩增的、储存的人类神经干细胞（HuCNS-SCs）被移植到新生或幼年 Shi-id 小鼠的大脑中的三个部位，这些小鼠分别无症状或表现出严重的低髓鞘形成。在这两组小鼠中，HuCNS-SCs 植入并优先分化为少突胶质细胞。这些少突胶质细胞产生了具有正常节段性组织、超微结构和轴突传导速度的致密髓鞘。通过定量组织病理学和高场离体磁共振成像发现，新生和幼年小鼠的髓鞘形成相当，通过分数各向异性值，在 HuCNS-SC 移植后 5 至 7 周显示 CNS 髓鞘形成。移植的 HuCNS-SCs 在中枢神经系统中产生了功能性髓鞘，即使在有严重症状性低髓鞘形成的动物中也是如此，这表明这种策略可能对治疗脱髓鞘疾病有用。
