Localization of bone marrow stromal cells to the injury site after intracerebral hemorrhage in rats.
OBJECTIVE
Previous studies demonstrated that intravascular injection of bone marrow stromal cells (BMSCs) significantly improved neurological functional recovery in a rat model of intracerebral hemorrhage (ICH). To further investigate the fate of transplanted cells, we examined the effect of male rat BMSCs administered to female rats after ICH.


METHODS
Twenty-seven female Wistar rats were subjected to ICH surgery. At 24 hours after ICH, these rats were randomly divided into 3 groups and injected intravenously with 1 ml phosphate-buffered saline or 0.5 million or 1 million male rat BMSCs in phosphate-buffered saline. To evaluate the neurological functional outcome, each rat was subjected to a series of behavioral tests (modified neurological severity score and corner turn test) at 1, 7, and 14 days after ICH. The rats were anesthetized intraperitoneally and killed, and the brain tissues were processed at Day 14 after ICH. Immunohistochemistry and in situ hybridization were used to identify cell-specific markers.


RESULTS
The male rat BMSCs significantly improved the neurological functional outcome and also significantly diminished tissue loss when intravenously transplanted into the rats after ICH. Immunoassay for bromodeoxyuridine (BrdU) and neuronal markers demonstrated a significant increase in the number of BrdU-positive cells, which indicated endogenous neurogenesis, and a significant increase in the number of cells positive for immature neuronal markers. In situ hybridization showed that more BMSCs resided around the hematoma of the rats treated with the 1-million-cell dose compared with the 0.5-million-cell-dose group. In addition, a subfraction of Y chromosome-positive cells were co-immunostained with the neuronal marker microtubule-associated protein-2 or the astrocytic marker glial fibrillary acidic protein.


CONCLUSIONS
Male rat BMSCs improve neurological outcome and increase histochemical parameters of neurogenesis when administered to female rats after ICH. This study has shown that the intravenously administered male rat BMSCs enter the brain, migrate to the perihematomal area, and express parenchymal markers.
Seyfried
Donald M
DM
Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan, USA.
Han
Yuxia
Y
Yang
Dongmei
D
Ding
Jennifer
J
Shen
Li Hong
LH
Savant-Bhonsale
Smita
S
Chopp
Michael
M
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods; D002465:Cell Movement; D002543:Cerebral Hemorrhage / Q000503:physiopathology* / Q000601:surgery*; D004195:Disease Models, Animal; D005260:Female; D006406:Hematoma / Q000503:physiopathology / Q000601:surgery; D007275:Injections, Intravenous; D008297:Male; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000637:transplantation*; D013997:Time Factors; D016896:Treatment Outcome