Traumatic brain injury (TBI) is a devastating neurological disorder, although the underlying pathophysiology is poorly understood. TBI causes blood–brain barrier (BBB) disruption, immune cell trafficking, neuroinflammation and neurodegeneration. CCL20 is an important chemokine mediating neuroinflammation. Human mesenchymal stem cell (hMSC) therapy is a promising regenerative approach but the inflammatory microenvironment in the brain tends to decrease the efficacy of the hMSC transplantation. Reducing the inflammation prior to hMSC therapy improves the outcome. We developed a combined nano-cell therapy by using dendrimers complexed with plasmids (dendriplexes) targeting CCL20 and its sole receptor CCR6 to reduce inflammation followed by hMSC transplantation. Treatment of TBI mice with shRNA conjugated dendriplexes followed by hMSC administration downregulated the inflammatory markers and significantly increased brain-derived neurotrophic factor (BDNF) expression in the cerebral cortex indicating future possible neurogenesis and improved behavioral deficits. Taken together, this nano-cell therapy ameliorates neuroinflammation and promotes brain tissue repair after TBI.

创伤性脑损伤 (TBI) 是一种破坏性的神经系统疾病，尽管其潜在的病理生理学知之甚少。TBI 会导致血脑屏障 (BBB) 破坏、免疫细胞运输、神经炎症和神经退行性变。CCL20是一种重要的介导神经炎症的趋化因子。人间充质干细胞 (hMSC) 疗法是一种有前途的再生方法，但大脑中的炎症微环境往往会降低 hMSC 移植的功效。在 hMSC 治疗之前减少炎症可以改善结果。我们开发了一种联合纳米细胞疗法，通过使用与靶向 CCL20 及其唯一受体 CCR6 的质粒（树状复合体）复合的树状大分子来减少炎症，然后进行 hMSC 移植。用 shRNA 缀合的树突复合物治疗 TBI 小鼠，然后给予 hMSC 下调炎症标志物并显着增加大脑皮层中脑源性神经营养因子 (BDNF) 的表达，表明未来可能的神经发生和改善的行为缺陷。总之，这种纳米细胞疗法可改善神经炎症并促进 TBI 后的脑组织修复。