Bone marrow stromal cell transplantation preserves gammaaminobutyric acid receptor function in the injured spinal cord.
A surprising shortage of information surrounds the mechanisms by which bone marrow stromal cells (BMSC) restore lost neurologic functions when transplanted into the damaged central nervous system. In the present study, we sought to elucidate whether BMSCs express the neuron-specific gamma-aminobutyric acid (GABA) receptor when transplanted into injured spinal cord. To examine this, we harvested and cultured rat femoral BMSCs. We then subjected Sprague-Dawley rats to thoracic spinal cord injury (SCI) with a pneumatic impact device. Fluorescence-labeled BMSCs (n = 7) were transplanted stereotactically or the vehicle in which these cells were cultured (n = 4) was introduced stereotactically into the rostral site of SCI at 7 days after injury. We evaluated GABA receptor function by measuring the binding potential for 125I-iomazenil (125I-IMZ) through in vitro autoradiography at 4 weeks after BMSC transplantation and simultaneously examined the fate of the transplanted BMSCs by immunocytochemistry. We found that the transplanted BMSC migrated toward the core of the injury and were densely distributed in the marginal region at 4 weeks after transplantation. BMSC transplantation significantly increased the binding potential for 125I-IMZ (p = 0.0376) and increased the number of GABA receptor-positive cells (p = 0.0077) in the marginal region of the injury site. Some of the transplanted BMSCs were positive for microtubule-associated protein-2 and the alpha1 subunit of GABA(A) receptor in the region of injury. These findings suggest that BMSCs have the potential to support the survival of neurons in the marginal region of SCI and can partly differentiate into neurons, regenerating spinal cord tissue at the site of injury.
Yano
Shunsuke
S
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Kuroda
Satoshi
S
Shichinohe
Hideo
H
Seki
Toshitaka
T
Ohnishi
Takako
T
Tamagami
Hiroshi
H
Hida
Kazutoshi
K
Iwasaki
Yoshinobu
Y
D000818:Animals; D001345:Autoradiography; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D007150:Immunohistochemistry; D009416:Nerve Regeneration / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
D011963:Receptors, GABA-A