Transplanted bone marrow stromal cells promote axonal regeneration and improve motor function in a rat spinal cord injury model.
OBJECTIVE
Recent studies have indicated that bone marrow stromal cells (BMSCs) have the potential to improve neurological function when transplanted into animal models of spinal cord injury (SCI). However, it is still unclear how the transplanted BMSCs promote functional recovery after SCI. In this study, therefore, we evaluated how the transplanted BMSCs restore the function of the dorsal corticospinal tracts in the injured spinal cord.


METHODS
The rats were subjected to incomplete SCI by means of a pneumatic impact device. BMSC or vehicle transplantation into the rostral site of SCI was performed at 7 days after injury. Neurological symptoms were assessed throughout the experiments. Fluoro-Ruby was injected into the dorsal funiculus of the rostral site of SCI at 63 days after injury. The fate of the transplanted BMSCs was examined using immunohistochemistry.


RESULTS
BMSC transplantation significantly enhanced functional recovery of the hind limbs. The number of Fluoro-Ruby-labeled fibers of the dorsal corticospinal tracts at the caudal site of SCI was significantly higher in the BMSC-transplanted animals than in the vehicle-transplanted animals. Some of the engrafted BMSCs were positive for Fluoro-Ruby, NeuN, and MAP2 in the gray matter, suggesting that they acquired neuronal phenotypes and built synaptic connection with the host's neural circuits. Others in the white matter morphologically simulated the astrocytes and were also positive for glial fibrillary acidic protein.


CONCLUSIONS
The findings suggest that the transplanted BMSCs acquire neural cell phenotypes around the injury site and contribute to rebuild the neural circuits, including the corticospinal tract, promoting functional recovery of the hind limbs.
Chiba
Yasuhiro
Y
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Kuroda
Satoshi
S
Maruichi
Katsuhiko
K
Osanai
Toshiya
T
Hokari
Masaaki
M
Yano
Shunsuke
S
Shichinohe
Hideo
H
Hida
Kazutoshi
K
Iwasaki
Yoshinobu
Y
D000818:Animals; D001369:Axons / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods*; D003911:Dextrans; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008124:Locomotion / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D012235:Rhodamines; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000601:surgery*; D018709:Statistics, Nonparametric; D017154:Stromal Cells / Q000502:physiology / Q000637:transplantation
D003911:Dextrans; C067661:Fluoro-Ruby; D005904:Glial Fibrillary Acidic Protein; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D012235:Rhodamines; D010751:Phosphopyruvate Hydratase