Abstract: Stem cell transplantation may represent a feasible therapeutic option for the recovery of neurological function in children with hypoxic-ischemic brain injury; however, the therapeutic efficacy of bone marrow-derived mesenchymal stem cells largely depends on the number of cells that are successfully transferred to the target. Magnet-targeted drug delivery systems can use a specific magnetic field to attract the drug to the target site, increasing the drug concentration. In this study, we found that the double-labeling using superparamagnetic iron oxide nanoparticle and poly-L-lysine (SPIO-PLL) of bone marrow-derived mesenchymal stem cells had no effect on cell survival but decreased cell proliferation 48 hours after labeling. Rat models of hypoxic-ischemic brain injury were established by ligating the left common carotid artery. One day after modeling, intraventricular and caudal vein injections of 1 × 105 SPIO-PLL-labeled bone marrow-derived mesenchymal stem cells were performed. Twenty-four hours after the intraventricular injection, magnets were fixed to the left side of the rats’ heads for 2 hours. Intravoxel incoherent motion magnetic resonance imaging revealed that the perfusion fraction and the diffusion coefficient of rat brain tissue were significantly increased in rats treated with SPIO-PLL-labeled cells through intraventricular injection combined with magnetic guidance, compared with those treated with SPIO-PLL-labeled cells through intraventricular or tail vein injections without magnetic guidance. Hematoxylin-eosin and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining revealed that in rats treated with SPIO-PLL-labeled cells through intraventricular injection under magnetic guidance, cerebral edema was alleviated, and apoptosis was decreased. These findings suggest that targeted magnetic guidance can be used to improve the therapeutic efficacy of bone marrow-derived mesenchymal stem cell transplantation for hypoxic-ischemic brain injury. This study was approved by the Animal Care and Use Committee of The Second Hospital of Dalian Medical University, China (approval No. 2016-060) on March 2, 2016.

Key words: bone marrow-derived mesenchymal stem cells, cell apoptosis, diffusion coefficient, cell labeling, intraventricular injection, intravoxel incoherent motion, magnetic guidance, perfusion fraction, superparamagnetic nanoparticles