Transplantation of galectin-1-expressing human neural stem cells into the injured spinal cord of adult common marmosets.
Delayed transplantation of neural stem/progenitor cells (NS/PCs) into the injured spinal cord can promote functional recovery in adult rats and monkeys. To enhance the functional recovery after NS/PC transplantation, we focused on galectin-1, a carbohydrate-binding protein with pleiotropic roles in cell growth, differentiation, apoptosis, and neurite outgrowth. Here, to determine the combined therapeutic effect of NS/PC transplantation and galectin-1 on spinal cord injury (SCI), human NS/PCs were transfected by lentivirus with galectin-1 and green fluorescent protein (GFP), (Gal-NS/PCs) or GFP alone (GFP-NS/PCs), expanded in vitro, and then transplanted into the spinal cord of adult common marmosets, 9 days after contusive cervical SCI. The animals' motor function was evaluated by their spontaneous motor activity, bar grip power, and performance on a treadmill test. Histological analyses revealed that the grafted human NS/PCs survived and differentiated into neurons, astrocytes, and oligodendrocytes. There were significant differences in the myelinated area, corticospinal fibers, and serotonergic fibers among the Gal-NS/PC, GFP-NS/PC, vehicle-control, and sham-operated groups. The Gal-NS/PC-grafted animals showed a better performance on all the behavioral tests compared with the other groups. These findings suggest that Gal-NS/PCs have better therapeutic potential than NS/PCs for SCI in nonhuman primates and that human Gal-NS/PC transplantation might be a feasible treatment for human SCI.
Yamane
Junichi
J
Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
Nakamura
Masaya
M
Iwanami
Akio
A
Sakaguchi
Masanori
M
Katoh
Hiroyuki
H
Yamada
Masayuki
M
Momoshima
Suketaka
S
Miyao
Sachiyo
S
Ishii
Ken
K
Tamaoki
Norikazu
N
Nomura
Tatsuji
T
Okano
Hirotaka James
HJ
Kanemura
Yonehiro
Y
Toyama
Yoshiaki
Y
Okano
Hideyuki
H
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002144:Callithrix / Q000601:surgery*; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D006085:Graft Survival / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D009416:Nerve Regeneration / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D010243:Paralysis / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D011712:Pyramidal Tracts / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D016896:Treatment Outcome
D037483:Galectin 1; D049452:Green Fluorescent Proteins