The effect of magnetic guiding BMSCs on hypoxic-ischemic brain damage via magnetic resonance imaging evaluation

Abstract

Hypoxic-ischemic brain damage (HIBD) is a critical disease in pediatric neurosurgery with high mortality rate and frequently leads to neurological sequelae. The role of bone marrow mesenchymal stem cells (BMSCs) in neuroprotection has been recognized. However, using the imaging methods to dynamically assess the neuroprotective effects of BMSCs is rarely reported. In this study, BMSCs were isolated, cultured and identified. Flow cytometry assay had shown the specific surface molecular markers of BMSCs, which indicated that the cultivated cells were purified BMSCs. The results demonstrated that CD29 and CD90 were highly expressed, whilst CD45 and CD11b were negatively expressed. Further, BMSCs were transplanted into Sprague Dawley (SD) rats established HIBD via three ways, including lateral ventricle (LV) injection, tail vein (TV) injection, and LV injection with magnetic guiding. Magnetic resonance imaging (MRI) was used to monitor and assess the treatment effect of super paramagnetic iron oxide (SPIO)-labeled BMSCs. The mean kurtosis (MK) values from diffusion kurtosis imaging (DKI) exhibited the significant differences. It was found that the MK value of HIBD group increased compared with that in Sham. At the meantime, the MK values of LV + HIBD, TV + HIBD and Magnetic+LV + HIBD groups decreased compared with that in HIBD group. Among these, the MK value reduced most significantly in Magnetic+LV + HIBD group. MRI illustrated that the treatment effect of Magnetic+LV + HIBD group was best. In addition, HE staining and TUNEL assay measured the pathological changes and apoptosis of brain tissues, which further verified the MRI results. All data suggest that magnetic guiding BMSCs, a targeted delivery way, is a new strategic theory for HIBD treatment. The DKI technology of MRI can dynamically evaluate the neuroprotective effects of transplanted BMSCs in HIBD.

Keywords: BMSCs; DKI; HIBD; MK; MRI; Magnetic guiding.