Science translational medicine · 2012
Human neural stem cells induce functional myelination in mice with severe dysmyelination.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Uchida Nobuko, Chen Kevin, Dohse Monika, Hansen Kelly D, Dean Justin, Buser Joshua R, Riddle Art, Beardsley Douglas J, Wan Ying, Gong Xi, Nguyen Thuan, Cummings Brian J, Anderson Aileen J, Tamaki Stanley J, Tsukamoto Ann, Weissman Irving L, Matsumoto Steven G, Sherman Larry S, Kroenke Christopher D, Back Stephen A
Аннотация
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.