Roles of ES cell-derived gliogenic neural stem/progenitor cells in functional recovery after spinal cord injury.
Transplantation of neural stem/progenitor cells (NS/PCs) following the sub-acute phase of spinal cord injury (SCI) has been shown to promote functional recovery in rodent models. However, the types of cells most effective for treating SCI have not been clarified. Taking advantage of our recently established neurosphere-based culture system of ES cell-derived NS/PCs, in which primary neurospheres (PNS) and passaged secondary neurospheres (SNS) exhibit neurogenic and gliogenic potentials, respectively, here we examined the distinct effects of transplanting neurogenic and gliogenic NS/PCs on the functional recovery of a mouse model of SCI. ES cell-derived PNS and SNS transplanted 9 days after contusive injury at the Th10 level exhibited neurogenic and gliogenic differentiation tendencies, respectively, similar to those seen in vitro. Interestingly, transplantation of the gliogenic SNS, but not the neurogenic PNS, promoted axonal growth, remyelination, and angiogenesis, and resulted in significant locomotor functional recovery after SCI. These findings suggest that gliogenic NS/PCs are effective for promoting the recovery from SCI, and provide essential insight into the mechanisms through which cellular transplantation leads to functional improvement after SCI.
Kumagai
Gentaro
G
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
Okada
Yohei
Y
Yamane
Junichi
J
Nagoshi
Narihito
N
Kitamura
Kazuya
K
Mukaino
Masahiko
M
Tsuji
Osahiko
O
Fujiyoshi
Kanehiro
K
Katoh
Hiroyuki
H
Okada
Seiji
S
Shibata
Shinsuke
S
Matsuzaki
Yumi
Y
Toh
Satoshi
S
Toyama
Yoshiaki
Y
Nakamura
Masaya
M
Okano
Hideyuki
H
D000818:Animals; D001369:Axons / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D017690:Cell Transplantation; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000628:therapy; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology*