Introduction: Traumatic brain injury (TBI) affects millions annually, often resulting in long-term neurodegeneration. Currently, no effective therapies exist to arrest or reverse this degeneration. Recent studies suggest that exosomes, nanoscale extracellular vesicles, could offer a neuroprotective treatment. Our preliminary data demonstrate that exosomes derived from human brain organoids show potent anti-inflammatory effects and improve memory function in a mild TBI mouse model. This study aims to further evaluate the therapeutic potential of brain organoid-derived exosomes for mitigating TBI-induced neuroinflammation and neurodegeneration.
Methods: We produced brain organoids from human iPSCs and isolated exosomes using ultracentrifugation. Mice subjected to mild TBI were treated with exosome injections on days 7, 14, and 21. Behavioral tests (rotarod, beam walk, and Barnes Maze) were conducted to assess motor function and memory. Histopathology of brain tissues focused on markers of neuroinflammation (GFAP, IBA1) and astrocyte polarization (A1/A2 phenotypes).
Results: Exosome-treated mice demonstrated memory function comparable to sham-operated controls, while untreated TBI mice exhibited significant memory deficits. Histopathology revealed increased hippocampal astrocytosis in treated mice, indicative of anti-inflammatory astrocyte polarization. No adverse effects were noted with exosome treatment.
Conclusion : Exosomes derived from human brain organoids demonstrate significant potential as a neuroprotective therapy for TBI, particularly in reducing neuroinflammation and preserving memory function. Further dose-ranging and safety studies are warranted to optimize this promising therapeutic approach.
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