Brain-derived neurotrophic factor gene-modified bone marrow mesenchymal stem cells in treatment of sciatic nerve injury / 中国组织工程研究

ABSTRACT

BACKGROUND: Peripheral nerve injuries are hoped to promote the regeneration of nerve repair by elevating brain-derived neurotrophic factor (BDNF) concentration in local injury regions. OBJECTIVE: To observe the recanalization of nerve fiber and motor function in sciatic nerve injury rats following BDNF gene-modified bone marrow mesenchymal stem cells (BMSCs). DESIGN, TIME AND SETTING: The randomized, controlled animal study was performed at the Fujian Institute of Neurology from May 2007 to May 2008. MATERIALS Femur and tibia of F344 male rats aged 2 months were sterilely harvested to prepare BMSCs. BDNF gene-modified BMSCs were prepared using constructed chronic viral vector PNL-BDNF-IRES2-EGFP. METHODS: The right sciatic nerve injury models were made using 60 adult Sprague Dawley rats. All models were randomly assigned into phosphate buffer saline (PBS) group, BMSC group and BDNF gene-modified BMSC group. 2 ?L BPS, 2 ?L BMSC solution and 2 ?L BDNF modified BMSC solution were separately transfered into injury site of each group. MAIN OUTCOME MEASURES: The retrograde horseradish peroxidase tracing was practiced to observe neural cell number in the Lumbar 4 and 5 spinal cord anterior horn at 2 and 4 weeks after microinjection. Sciatic nerve function index was used to observe rat motor function of injured limbs. Fluorescence excitation and immunohistochemistry were employed to detect BMSC survival and BDNF expression. RESULTS: Cell number was more, and nerve function recovery was better in the Lumbar 4 and 5 spinal cord anterior horn in the BDNF gene-modified BMSC group than in the PBS and BMSC groups. BMSC survival was found in the injured sites in the BMSC and BDNF gene-modified BMSC groups. BDNF expression was significantly more in the BDNF gene-modified BMSC group than in the BMSC group. CONCLUSION: BDNF gene-modified BMSCs have promotion effects on the recanalization and functional recovery of nerve fiber following peripheral nerve injury.