Transplantation of embryonic stem cell-derived neural stem cells for spinal cord injury in adult mice.
OBJECTIVE
To investigate the efficacy of embryonic stem cell-derived neural stem cells (NSCs) for spinal cord injury (SCI) in mice and whether a combination treatment with thyroid hormone provides a more effective ES cell-based therapy.


METHODS
Nestin-positive NSCs were induced from undifferentiated mouse ES cells by a step-by-step culture and used as grafts. Thirty-six mice were subjected to an SCI at Th10 and divided into three groups of 12. Graft cells were transplanted into the injury site 10 days after injury. Group 1 mice were left under observation without receiving graft cells, while mice in Group 2 received 2 x 104 graft cells, and those in Group 3 received 2 x 104 graft cells and were treated with a continuous intraperitoneal injection of thyroxin using osmotic mini-pumps. Behavioral improvement was assessed by a scoring system throughout the experimental period until post-transplantation day (PD) 28.


RESULTS
Mice in Groups 2 and 3 demonstrated an improved behavioral function, as compared to those in Group 1 after PD 14. There was no significant difference in behavioral recovery between Groups 2 and 3.


CONCLUSIONS
Transplantation of ES-NSCs into the injury site was effective for SCI, while thyroxine did not deliver additional effectiveness.
Kimura
Hajime
H
Department of Neurosurgery, Nara Medical University, Nara, Japan.
Yoshikawa
Masahide
M
Matsuda
Ryousuke
R
Toriumi
Hayato
H
Nishimura
Fumihiko
F
Hirabayashi
Hidehiro
H
Nakase
Hiroyuki
H
Kawaguchi
Shoichiro
S
Ishizaka
Shigeaki
S
Sakaki
Toshisuke
T
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line / Q000637:transplantation; D003131:Combined Modality Therapy; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D015918:Infusion Pumps, Implantable; D007381:Intermediate Filament Proteins / Q000032:analysis; D051379:Mice; D009419:Nerve Tissue Proteins / Q000032:analysis; D064231:Nestin; D009474:Neurons / Q000166:cytology / Q000473:pathology; D009836:Oligodendroglia / Q000737:chemistry / Q000473:pathology; D011897:Random Allocation; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D033581:Stem Cell Transplantation; D013974:Thyroxine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D013974:Thyroxine