129 Genetically Engineered Exosomes Derived From Mesenchymal Stromal Cells Promote Functional and Structural Recovery in Rats After Traumatic Brain Injury. (April 2023)

• Record Type: Journal Article
• Authors: Mahmood, Asim; Zhang, Yanlu; Zhang, Yi; Chopp, Michael; Xiong, Ye
• Is Part Of: Neurosurgery. Volume 69(2023)Supplement 1
• Page Start: 32
• Page End: 32
• Publication Date: 2023-04
• Subjects: Nervous system -- Surgery -- Periodicals; 617.48005
• DOI: 10.1227/neu.0000000000002375_129
• Languages: English
• ISSNs: 0148-396X

Abstract

Abstract : INTRODUCTION: Previous studies have demonstrated that multi-potent mesenchymal stromal cell (MSC)-derived exosomes improve functional recovery after experimental traumatic brain injury (TBI). Our present research focuses on augmenting the beneficial effects of exosomes by transfecting them with microRNAs. METHODS: Adult male rats were injured with controlled cortical impact. Animals received a single intravenous injection of MiR-17-92 cluster-enriched exosomes (100 µg/rat) or control exosomes (100 µg/rat) or Vehicle (phosphate-buffered solution) one day after injury. A battery of neurological functional tests was performed after TBI. Spatial learning and memory were measured using the Morris water maze test. All animals were sacrificed five weeks after injury. Their brains were processed for histopathological and immunohistochemical analysis of cell loss, angiogenesis, neurogenesis, and neuroinflammation. RESULTS: Compared with control, both Exo-17-92 and Exo-empty treatments significantly improved sensorimotor and cognitive function, reduced neuroinflammation and hippocampal neuronal cell loss, and promoted angiogenesis and neurogenesis (p < 0.05). Moreover, Exo-17-92 treatment exhibited a significantly more robust effect in improving functional recovery and in reducing cell loss, and enhancing angiogenesis and neurogenesis compared to Exo-empty treatment (p<0.05). CONCLUSIONS: Exosomes enriched with miR-17-92 cluster have a significantly better effect on improving functional recovery after TBI compared with Exo-empty treatment, likely by enhancing endogenous angiogenesis and neurogenesis. Engineering specific miRNA in exosomes may provide a novel therapeutic strategy for the management of TBI.