Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice.
We report that prospectively isolated, human CNS stem cells grown as neurospheres (hCNS-SCns) survive, migrate, and express differentiation markers for neurons and oligodendrocytes after long-term engraftment in spinal cord-injured NOD-scid mice. hCNS-SCns engraftment was associated with locomotor recovery, an observation that was abolished by selective ablation of engrafted cells by diphtheria toxin. Remyelination by hCNS-SCns was found in both the spinal cord injury NOD-scid model and myelin-deficient shiverer mice. Moreover, electron microscopic evidence consistent with synapse formation between hCNS-SCns and mouse host neurons was observed. Glial fibrillary acidic protein-positive astrocytic differentiation was rare, and hCNS-SCns did not appear to contribute to the scar. These data suggest that hCNS-SCns may possess therapeutic potential for CNS injury and disease.
Cummings
Brian J
BJ
Department of Physical Medicine and Rehabilitation, Reeve-Irvine Research Center, University of California, Irvine, CA 92697, USA. cummings@uci.edu
Uchida
Nobuko
N
Tamaki
Stanley J
SJ
Salazar
Desirée L
DL
Hooshmand
Mitra
M
Summers
Robert
R
Gage
Fred H
FH
Anderson
Aileen J
AJ
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009043:Motor Activity; D009474:Neurons / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D013116:Spinal Cord / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology* / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure