Protective Effect of Mesenchymal Stromal Cell-Derived Exosomes on Traumatic Brain Injury via miR-216a-5p

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 brain-derived neurotrophic factor (BDNF)-induced MSCs-Exo can effectively promote functional recovery and neurogenesis in rats after TBI. MATERIAL/METHODS: BM-MSCs of rats were extracted by whole bone marrow culture, BDNF was added to BM-MSCs as an intervention, supernatant was collected, and exosomes were separated and purified by ultracentrifugation. Exosomes were identified by Western blot (WB), transmission electron microscopy (TEM), and particle size analysis and were subsequently used in cell and animal experiments. The experimental animals were divided into a sham group, a PBS group, an MSCs-Exo group, and a BDNF-induced MSCs-Exo group (n=12). An electric cortical contusion impactor (eCCI) was used to cause TBI in all rats except the sham group. We investigated the recovery of sensorimotor function and spatial learning ability, inflammation inhibition, and neuron regeneration in rats after TBI. RESULTS: Compared with the MSCs-Exo group, the BDNF-induced MSCs-Exo group showed better effects in promoting the recovery of sensorimotor function and spatial learning ability. BDNF-induced MSCs-Exo successfully inhibited inflammation and promoted neuronal regeneration in vivo and in vitro. We further analyzed miRNAs in BDNF-induced MSCs-Exo and MSCs-Exo and found that the expression of miR-216a-5p in BDNF-induced MSCs-Exo was significantly higher than that in MSCs-Exo as determined by qRT-PCR. Rescue experiments indicated that miR-216a-5p had a similar function as BDNF-induced MSCs-Exo. CONCLUSIONS: We found that BDNF-induced MSCs-Exo can improve cell migration and inhibit apoptosis better than MSCs-Exo in rats after TBI, and the mechanism may be related to the high expression of miR-216a-5p.