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09 March 2020 : Animal Research  

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

Huiyou Xu12ABCDE, Zhilong Jia1EG, Ke Ma12BCDF, Jian Zhang12BCDF, Chen Dai12BCD, Zitong Yao12BCD, Wusheng Deng12BCD, Jianzhong Su1EG, Renjie Wang1ABCDFG, Xuyi Chen1BCDG*

DOI: 10.12659/MSM.920855

Med Sci Monit 2020; 26:e920855

Abstract

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 METHODS: 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.

Keywords: Brain Injuries, mesenchymal stromal cells, MicroRNAs, Apoptosis, Brain, Brain Injuries, Traumatic, Brain-Derived Neurotrophic Factor, Cell Movement, Culture Media, Disease Models, Animal, exosomes, Male, Nerve Regeneration, neurogenesis, Neurons, primary cell culture, Rats

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750