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Protective effect of BMSCs-derived exosomes mediated by BDNF on TBI via miR-216a-5p

Huiyou XuDepartment of Neurosurgery, Characteristic Medical Center of Chinese People’s Armed Police Force; Institution of Brain Trauma and Neurology Disease of People’s Armed Police Forces; Tianjin Key Laboratory of Neurotrauma Repair, Tianjin, China (mainland)Zhilong JiaDepartment of Neurosurgery, Characteristic Medical Center of Chinese People’s Armed Police Force; Institution of Brain Trauma and Neurology Disease of People’s Armed Police Forces; Tianjin Key Laboratory of Neurotrauma Repair, Tianjin, China (mainland)Ke MaDepartment of Neurosurgery, Characteristic Medical Center of Chinese People’s Armed Police Force; Institution of Brain Trauma and Neurology Disease of People’s Armed Police Forces; Tianjin Key Laboratory of Neurotrauma Repair, Tianjin, China (mainland)Jian ZhangDepartment of Neurosurgery, Characteristic Medical Center of Chinese People’s Armed Police Force; Institution of Brain Trauma and Neurology Disease of People’s Armed Police Forces; Tianjin Key Laboratory of Neurotrauma Repair, Tianjin, China (mainland)Chen DaiDepartment of Neurosurgery, Characteristic Medical Center of Chinese People’s Armed Police Force; Institution of Brain Trauma and Neurology Disease of People’s Armed Police Forces; Tianjin Key Laboratory of Neurotrauma Repair, Tianjin, China (mainland)Zitong YaoDepartment of Neurosurgery, Characteristic Medical Center of Chinese People’s Armed Police Force; Institution of Brain Trauma and Neurology Disease of People’s Armed Police Forces; Tianjin Key Laboratory of Neurotrauma Repair, Tianjin, China (mainland)Wu-Sheng DengDepartment of Neurosurgery, Characteristic Medical Center of Chinese People’s Armed Police Force; Institution of Brain Trauma and Neurology Disease of People’s Armed Police Forces; Tianjin Key Laboratory of Neurotrauma Repair, Tianjin, China (mainland)Jianzhong SuDepartment of Neurosurgery, Characteristic Medical Center of Chinese People’s Armed Police Force; Institution of Brain Trauma and Neurology Disease of People’s Armed Police Forces; Tianjin Key Laboratory of Neurotrauma Repair, Tianjin, China (mainland)Renjie WangDepartment of Neurosurgery, Characteristic Medical Center of Chinese People’s Armed Police Force; Institution of Brain Trauma and Neurology Disease of People’s Armed Police Forces; Tianjin Key Laboratory of Neurotrauma Repair, Tianjin, China (mainland)Xuyi ChenDepartment of Neurosurgery, Characteristic Medical Center of Chinese People’s Armed Police Force; Institution of Brain Trauma and Neurology Disease of People’s Armed Police Forces; Tianjin Key Laboratory of Neurotrauma Repair, Tianjin, China (mainland)
2020en
ABI

Аннотация

BACKGROUND Transplantation of exosomes derived from mesenchymal stem cells (MSCs-Exo) can improve the recovery of neurological function in rats after traumatic brain injury (TBI). We tested a new hypothesis that BDNF-mediated MSCs-Exo could effectively promote functional recovery and neurogenesis of rats after TBI. MATERIAL AND METHOD BMSCs of rats were extracted by whole bone marrow culture, BDNF was added to BMSCs for intervention, supernatant was collected, and exosomes were separated and purified by hypercentrifugation. Exosomes were identified by WB, TEM and particle size analysis and subsequently used in cell and animal experiments. We investigated the recovery of sensorimotor function and spatial learning ability, inflammation inhibition and neuron regeneration in rats after TBI. RESULTS Compared with group MSCs-Exo, group BDNF-mediated MSCs-Exo showed better effects in promoting the recovery of sensorimotor function and spatial learning ability. BDNF-mediated MSCs-Exo successfully inhibited inflammation and promoted neuronal regeneration in vivo and in vitro. We further analyzed miRNA in BDNF-mediated MSCs-Exo and MSCs-Exo, and found that the expression of miR-216a-5p in BDNF-mediated MSCs-Exo was significantly higher than that in MSCs-Exo by qRT-PCR. Rescue experiment indicated that miR-216a-5p has a similar function to BDNF-mediated MSCs-Exo. CONCLUSIONS In conclusion, we found that BDNF-mediated MSCs-Exo can better promote neurogenesis and inhibit apoptosis than MSCs-Exo in rats after TBI, and the mechanism may be related to the high expression of miR-216a-5p.

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