Human marrow stromal cell treatment provides long-lasting benefit after traumatic brain injury in rats.
OBJECTIVE
This study was designed to investigate the effects of human bone marrow stromal cell (hMSC) administration in rats for 3 months after traumatic brain injury (TBI).


METHODS
Adult male Wistar rats (n = 60) were injured with controlled cortical impact and divided into four groups. The three treatment groups (n = 10 each) were injected with 2 x 10, 4 x 10, and 8 x 10 hMSCs, respectively, intravenously, whereas the control group (n = 30) received phosphate-buffered saline. All injections were performed 1 day after injury into the tail veins of rats. Neurological functional evaluation of animals was performed before and after injury by use of Neurological Severity Scores. Animals were sacrificed 3 months after TBI, and brain sections were stained by immunohistochemistry.


RESULTS
Statistically significant improvement in functional outcome was observed in all three treatment groups compared with control values (P < 0.05). This benefit was visible 14 days after TBI and persisted until 3 months (end of trial). There was no difference in functional outcome among the three treatment groups. Histological analysis showed that hMSCs were present in the lesion boundary zone at 3 months with all three doses tested.


CONCLUSIONS
hMSCs injected in rats after TBI survive until 3 months and provide long-lasting functional benefit. Functional improvement may be attributed to stimulation of endogenous neurorestorative functions such as neurogenesis and synaptogenesis.
Mahmood
Asim
A
Department of Neurosurgery, Henry Ford Hospital, Detroit, Michigan 48202, USA. nsaam@neuro.hfh.edu
Lu
Dunyue
D
Qu
Changsheng
C
Goussev
Anton
A
Chopp
Michael
M
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D001930:Brain Injuries / Q000503:physiopathology / Q000601:surgery*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009460:Neurologic Examination / Q000379:methods; D009687:Nuclear Proteins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology*; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D009687:Nuclear Proteins; C007293:DAPI; D010751:Phosphopyruvate Hydratase