The Neovascularization Effect of Bone Marrow Stromal Cells in Temporal Muscle after Encephalomyosynangiosis in Chronic Cerebral Ischemic Rats

OBJECTIVE: In Moyamoya disease, the primary goal of treatment is to improve collateral circulation through angiogenesis. In the present study, we obtained and sub-cultured bone marrow stromal cells (BMSCs) from rats without a cell-mediated immune response. Then, we injected the labeled BMSCs directly into adjacent temporal muscle during encephalomyosynangiosis (EMS). Three weeks after BMSC transplantation, we examined the survival of the cells and the extent of neovascularization. METHODS: We divided 20 rats into a BMSC transplantation group (n=12) and a control group (n=8). Seven days after the induction of chronic cerebral ischemia, an EMS operation was performed, and labeled BMSCs (1x106(6)/100 microliter) were injected in the temporal muscle for the transplantation group, while an equivalent amount of culture solution was injected for the control group. Three weeks after the transplantation, temporal muscle and brain tissue were collected for histological examination and western blot analysis. RESULTS: The capillary/muscle ratio in the temporal muscle was increased in the BMSC transplantation group compared to the control group, showing a greater increase of angiogenesis (p<0.05). In the brain tissue, angiogenesis was not significantly different between the two groups. The injected BMSCs in the temporal muscle were vascular endothelial growth factor (VEGF)-positive by immunofluorescence staining. In both temporal muscle and brain tissue, the expression of VEGF by western blot analysis was not much different between the two groups. CONCLUSION: During EMS in a chronic cerebral ischemia rat model, the injection of BMSCs resulted in accelerated angiogenesis in the temporal muscle compared to the control group.

The Survival and Migration Pattern of the Bone Marrow Stromal Cells after Intracerebral Transplantation in Rats

OBJECTIVE: Bone marrow stromal cells (MSCs) are stem cells that can differentiate into chondrogenic, osteogenic, myogenic, adipogenic, and neurogenic cells according to the surrounding environment. Moreover, transplanted stem cells can migrate from the graft site in the recipient brain. The survival and migration patterns of the transplanted MSCs are investigated histologically. METHODS: Bone MSCs were harvested from adult Fisher rats and cultured for several passages. To identify cells derived from MSCs, 5microM bromodeoxyuridine (BrdU) was added to the medium 72 hours before transplantation. Bone MSCs were transplanted into the striatum of the recipient rat stereotactically. Test groups consisted of intracerebral transplantation of MSCs (n=6) and control-cultured medium alone (n=4). BrdU, hematoxylin and eosin staining were performed fourteen days after transplantation. RESULTS: More than 80% of the cultured MSCs showed reactivity to BrdU in vitro. Transplanted MSCs were found mainly around the injection route and migrated from the injection site about 1mm along the white matter. The corpus callosum clearly showed migration of MSCs. CONCLUSION: The results suggest that stem cells can be easily obtained from the adult bone MSCs and the transplanted MSCs can migrate from the grafted site. In such cases, the migration pattern of the grafted MSCs may be determined according to the recipient environment.