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(6), 4 X 10(6), and 8 X 10(6) 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 immunohistochernistry. 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. CONCLUSION: 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.