Effects of intravenous administration of human bone marrow stromal cells after intracerebral hemorrhage in rats.
OBJECTIVE
The goal of this study was to investigate whether human bone marrow stromal cells (hBMSCs) administered by intravenous injection have a beneficial effect on outcome after intracerebral hemorrhage (ICH) in rats.


METHODS
An ICH was induced in 54 adult male Wistar rats by a stereotactically guided injection of autologous blood into the right striatum. Intravenous infusion of the hBMSCs (3, 5, or 8 million cells) was performed 1 day after ICH, and for each dose group there was a control group that received injections of vehicle. Neurological function, which was evaluated using the Neurological Severity Score (NSS) and the corner turn test, was tested before and at 1, 7, and 14 days after ICH. After 14 days of survival, the area of encephalomalacia was calculated and histochemical labeling was performed. For all three groups, there were no statistical differences in either the NSS or corner turn tests after 1 day. After 7 and 14 days, however, the three groups that received the hBMSCs showed significant improvement in functional scores compared with the control group. In addition, after 14 days there was significantly more striatal tissue loss in the placebo groups compared with each of the three treatment groups. The region of injury in the treated animals demonstrated a significantly increased presence of hBMSCs, immature neurons, neuronal migration, synaptogenesis, and newly formed DNA.


CONCLUSIONS
Intravenous administration of hBMSCs significantly improves neurological function in rats subjected to ICH. This improvement in the treated animals is associated with reduced tissue loss and increased local presence of the hBMSCs, mitotic activity, immature neurons, synaptogenesis, and neuronal migration.
Seyfried
Donald
D
Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan 48202, USA. nsdos@neuro.hfh.edu
Ding
Jennifer
J
Han
Yuxia
Y
Li
Yi
Y
Chen
Jieli
J
Chopp
Michael
M
D000818:Animals; D001522:Behavior, Animal; D001854:Bone Marrow Cells; D002465:Cell Movement; D006801:Humans; D007262:Infusions, Intravenous; D020300:Intracranial Hemorrhages / Q000628:therapy*; D008297:Male; D009474:Neurons; D010919:Placebos; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D012720:Severity of Illness Index; D017154:Stromal Cells; D016896:Treatment Outcome
D010919:Placebos