Comparison between fetal spinal-cord- and forebrain-derived neural stem/progenitor cells as a source of transplantation for spinal cord injury.
Recently, we have shown that the transplantation of spinal-cord-derived neural stem/progenitor cells (NSPCs) can contribute to the repair of injured spinal cords in adult rats, which may correspond to a behavioral recovery. To apply these results to clinical practice, a system for supplying human NSPCs on a large scale must be established. However, human spinal-cord-derived NSPCs are known to have a low proliferation rate, compared with forebrain-derived NSPCs. This low proliferative potency limits the feasibility of large-scale spinal cord-derived NSPC use. Thus, forebrain-derived NSPCs should be examined as an alternative to spinal-cord-derived NSPCs for the treatment of spinal cord injuries. In this study, we compared spinal-cord- and forebrain-derived NSPCs transplanted into injured spinal cords with respect to their fates in vivo as well as the animals' functional recovery. Both spinal-cord- and forebrain-derived NSPCs promoted functional recovery in rats with spinal cord injuries. While both spinal-cord- and forebrain-derived NSPCs survived, migrated and differentiated into neurons, astrocytes and oligodendrocytes in response to the microenvironment within the injured spinal cord after transplantation, forebrain-derived NSPCs differentiated into more neurons and fewer oligodendrocytes, compared to spinal-cord-derived NSPCs. Neurons that had differentiated from the transplanted forebrain-derived NSPCs were shown to be positive for neurotransmitters like GABA, glutamate and glycine, although authentic glycinergic neurons are not normally present within the forebrain. Thus, at least a subpopulation of the transplanted forebrain-derived NSPCs differentiated into spinal-cord-type neurons. In conclusion, forebrain-derived NSPCs could be used as an alternative to spinal-cord-derived NSPCs as a potential therapeutic agent for spinal cord injuries.
Watanabe
Kota
K
Department of Orthopaedic Surgery, Keio University, Tokyo, Japan.
Nakamura
Masaya
M
Iwanami
Akio
A
Fujita
Yuko
Y
Kanemura
Yonehiro
Y
Toyama
Yoshiaki
Y
Okano
Hideyuki
H
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D010641:Phenotype; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000637:transplantation*; D013119:Spinal Cord Injuries / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D016896:Treatment Outcome
D018377:Neurotransmitter Agents