Therapeutic benefit of intrathecal injection of marrow stromal cells on ischemia-injured spinal cord.
BACKGROUND
Prophylactic transplantation of marrow stromal cells (MSCs) before spinal cord ischemia has been shown to attenuate neurologic injures. We sought to investigate the therapeutic effect of MSCs on ischemia-injured spinal cord.


METHODS
Marrow stromal cells were expanded in vitro and prelabeled with bromodeoxyuridine. Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Four groups were enrolled. About 1 x 10(8) MSCs were intrathecally injected 2 hours (group MSC-2h), 24 hours (group MSC-24h), or 48 hours (group MSC-48h) after spinal cord ischemia, respectively. The control group received intrathecal injection of medium alone. Hind-limb motor function was assessed during a 28-day recovery period with Tarlov criteria, and then histologic examination was performed.


RESULTS
Marrow stromal cells still could be found in the spinal cord 4 weeks after transplantation. The capillary density in the ventral gray matter was significantly increased in the three MSC-treated groups (p < 0.01 versus control group, respectively). After a 28-day recovery, marked functional improvement was detected in group MSC-2h (from day 1 to 28, p < 0.05, versus control group, respectively) and group MSC-24h (from day 14 to 28, p < 0.05, versus control group, respectively), but not in group MSC-48h. The number of intact motor neurons was much greater in group MSC-2h (p < 0.05, versus control group).


CONCLUSIONS
Intrathecal injection of MSCs enhances angiogenesis in the host spinal cord and improves the motor functional recovery after spinal cord ischemia. The therapeutic time window is critical for the therapeutic effect of MSCs.
Shi
Enyi
E
Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, China. shienyi2002@hotmail.com
Kazui
Teruhisa
T
Jiang
Xiaojing
X
Washiyama
Naoki
N
Yamashita
Katsushi
K
Terada
Hitoshi
H
Bashar
Abul Hasan Muhammad
AH
D000818:Animals; D001707:Biopsy, Needle; D016026:Bone Marrow Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007278:Injections, Spinal; D018919:Neovascularization, Physiologic; D009460:Neurologic Examination; D011817:Rabbits; D011897:Random Allocation; D020127:Recovery of Function; D012016:Reference Values; D012680:Sensitivity and Specificity; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*; D020760:Spinal Cord Ischemia / Q000473:pathology / Q000628:therapy*; D017154:Stromal Cells / Q000637:transplantation; D014182:Transplantation, Autologous