Human neural stem cells induce functional myelination in mice with severe dysmyelination.
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.
StemCells Inc., Newark, CA 94560, USA. nobuko.uchida@stemcellsinc.com
Nobuko
N
Uchida
Kevin
K
Chen
Monika
M
Dohse
Kelly D
KD
Hansen
Justin
J
Dean
Joshua R
JR
Buser
Art
A
Riddle
Douglas J
DJ
Beardsley
Ying
Y
Wan
Xi
X
Gong
Thuan
T
Nguyen
Brian J
BJ
Cummings
Aileen J
AJ
Anderson
Stanley J
SJ
Tamaki
Ann
A
Tsukamoto
Irving L
IL
Weissman
Steven G
SG
Matsumoto
Larry S
LS
Sherman
Christopher D
CD
Kroenke
Stephen A
SA
Back
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D003711:Demyelinating Diseases / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology; D033581:Stem Cell Transplantation