Mir-17-92 cluster-enriched exosomes improve tissue and functional recovery in rats after traumatic brain injury
Zhang Y, Zhang Y, Chopp M, Pang H, Zhang ZG, Mahmood A, and Xiong Y. Mir-17-92 cluster-enriched exosomes improve tissue and functional recovery in rats after traumatic brain injury. J Neurotrauma 2021; 38(14):A112-A113.
Exosomes play an important role in intercellular communication by delivering microRNAs to recipient cells. Previous studies have demonstrated that multipotent mesenchymal stromal cell (MSC)-derived exosomes improve functional recovery after experimental traumatic brain injury (TBI). This study was performed to determine whether treatment of TBI with miR-17-92 cluster-enriched exosomes (Exo-17-92) harvested from human bone marrow MSCs transfected with a miR-17-92 cluster plasmid enhances tissue and neurological recovery compared to exosomes derived from MSCs transfected with an empty plasmid vector (Exo-empty). Adult male rats were subjected to a unilateral moderate cortical contusion. Animals received a single intravenous injection ofmiR-17-92 cluster-enriched exosomes (100 lg/rat, Exo-17-92) or control exosomes (100 lg/rat, Exoempty) or Vehicle (phosphate-buffered solution) 1 day after injury. A battery of neurological functional tests were performed weekly after TBI for 5 weeks. Spatial learning and memory were measured on days 31-35 after TBI using the Morris water maze test. All animals were sacrificed 5 weeks after injury. Their brains were processed for histopathological and immunohistochemical analyses of lesion volume, cell loss, angiogenesis, neurogenesis and neuroinflammation. Compared to the vehicle, both Exo-17-92 and Exo-empty treatments significantly improved sensorimotor and cognitive function, reduced neuroinflammation and hippocampal neuronal cell loss, promoted angiogenesis and neurogenesis without altering the lesion volume. Moreover, Exo-17-92 treatment exhibited a significantly more robust therapeutic effect on improvement in functional recovery by reducing neuroinflammation and cell loss, enhancing angiogenesis and neurogenesis than did Exo-empty treatment. In conclusion, exosomes enriched with miR-17-92 cluster have a significantly better effect on im-proving functional recovery after TBI compared to Exo-empty, likely by reducing neuroinflammation and enhancing endogenous angiogenesis and neurogenesis. Engineering specific miRNA in exosomes may provide a novel therapeutic strategy for treatment of TBI.