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Ultrasound-targeted microbubble enhances migration and therapeutic efficacy of marrow mesenchymal stem cell on rat middle cerebral artery occlusion stroke model
Authors:Jian Qian  Luna Wang  Qiming Li  Dujuan Sha  Jun Wang  Jun Zhang  Peng Xu  Guofeng Fan
Institution:Department of Emergency Medicine, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, China
Abstract:To investigate the role of ultrasound-targeted microbubbles in the homing effect of bone marrow-derived mesenchymal stem cells (BMSCs) and in the therapeutic efficacy of BMSCs on the ischemic stroke. A middle cerebral artery occlusion (MCAO) model was induced by plug wire preparation. Seventy-two hours after MCAO, the treatment of BMSCs with ultrasound-targeted microbubble was assessed via modified neurological severity score (mNSS), infarct volumes, and cerebral edema. In addition, immunofluorescence was performed to analyze the homing effect of BMSCs with ultrasound-targeted microbubble. We find that BMSCs with ultrasound-targeted microbubble (BMMSCs with ultrasound-targeted microbubble USMM] group) could significantly ameliorate mNSS, infarct volumes, and cerebral edema of MCAO compared with phosphate buffer saline group, BMSCs alone group (BMSC group), and BMSCs with Ultrasound group (Ultrasound group). Immunofluorescence analysis demonstrated that ultrasound-targeted microbubbles promoted the accumulation of BMSCs in rat MCAO brains. Our findings demonstrated that ultrasound-targeted microbubble could be an effective approach for the accumulation of BMSCs on ischemic stroke, and further improved the therapeutic efficacy of BMSCs on MCAO.
Keywords:bone marrow-derived mesenchymal stem cells  ischemic stroke  middle cerebral artery occlusion  ultrasound-mediated microbubble
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