Intravenously transplanted human neural stem cells migrate to the injured spinal cord in adult mice in an SDF-1- and HGF-dependent manner.
Neural stem cell (NSC) transplantation has exhibited considerable therapeutic potential in spinal cord injury. However, most experiments in animals have been performed by injecting these cells directly into the injured spinal cord. A cardinal feature of NSCs is their exceptional migratory ability through the nervous system. Based on the migratory ability of NSCs, we investigated whether minimally invasive intravenous delivery of NSCs could facilitate their migration to the injured spinal cord and identified the chemo-attractants secreted by the lesions. Nude mice were injected intravenously with labelled human NSCs at 3, 7 and 10 days after the compression of the spinal cord at the T8 level. The migration of NSCs to the lesioned spinal cord was highest at 7 days after injury; this correlated with the peak of hepatocyte growth factor and stromal cell-derived factor-1 mRNA expressions in the lesion but not with the disruption of the blood-brain barrier. Finally, the grafted NSCs differentiated into neuronal and glial subpopulations at 21 days after transplantation. Our study suggests that intravenously administered NSCs can be employed as a renewable source for replacing lost cells for the treatment of spinal cord injuries.
Takeuchi
Hiroki
H
Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
Natsume
Atsushi
A
Wakabayashi
Toshihiko
T
Aoshima
Chihiro
C
Shimato
Shinji
S
Ito
Motokazu
M
Ishii
Jun
J
Maeda
Yuka
Y
Hara
Masahito
M
Kim
Seung U
SU
Yoshida
Jun
J
D000596:Amino Acids; D000818:Animals; D001522:Behavior, Animal; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D004195:Disease Models, Animal; D005333:Fetus; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous / Q000379:methods; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000379:methods
D000596:Amino Acids; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; C098463:dolaisoleucine; D017228:Hepatocyte Growth Factor