Role of SDF-1/CXCR4 system in survival and migration of bone marrow stromal cells after transplantation into mice cerebral infarct

Abstract

Recent studies have indicated that bone marrow stromal cells (BMSC) have the potential to improve neurological function when transplanted into animal models of cerebral infarction. However, it is still obscure how the transplanted BMSC restore the lost neurological function. In this study, therefore, we aimed to elucidate the role of stromal cell-derived factor-1 (SDF-1) and its specific receptor, CXCR4, in BMSC transplantation into the brain subjected to cerebral infarction. The BMSC were harvested from the wild type (WT) and CXCR4-knockout (CXCR4-KO) mice and were cultured. The mice were subjected to permanent middle cerebral artery occlusion. The WT or CXCR4-KO BMSC was injected into the ipsilateral striatum 7 days after the insult. Motor function of the animals was serially evaluated, using a rotarod treadmill. Using fluorescence immunohistochemistry, we evaluated the distribution and phenotype of the transplanted cells 4 weeks after transplantation. Recovery of motor function in the WT BMSC-transplanted mice was more pronounced than in the CXCR4-KO-transplanted mice and the vehicle-treated ones. SDF-1 was extensively expressed in peri-infarct area. In the WT BMSC-transplanted mice, the transplanted cells were extensively distributed in the ipsilateral hemisphere, and many of them migrated towards the peri-infarct area and expressed the proteins specific for neurons and astrocytes, although these findings were not observed in the CXCR4-KO-transplanted mice. The results suggest that the SDF-1/CXCR4 system may play a critical role in the survival, proliferation and migration of the transplanted BMSC and contribute to recovery of neurological function.