TY - JOUR TI - Treatment with shCCL20-CCR6 nanodendriplexes and human mesenchymal stem cell therapy improves pathology in mice with repeated traumatic brain injury AU - Mayilsamy, Karthick AU - Markoutsa, Eleni AU - Das, Mahasweta AU - Chopade, Pratik AU - Puro, Durga AU - Kumar, Akanksha AU - Gulick, Danielle AU - Willing, Alison E. AU - Mohapatra, Shyam S AU - Mohapatra, Subhra T2 - Nanomedicine: Nanotechnology, Biology and Medicine AB - 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. DA - 2020/06/26/ PY - 2020 DO - 10.1016/j.nano.2020.102247 DP - ScienceDirect SP - 102247 J2 - Nanomedicine: Nanotechnology, Biology and Medicine LA - en SN - 1549-9634 UR - http://www.sciencedirect.com/science/article/pii/S1549963420301015 Y2 - 2020/07/06/18:27:15 KW - BDNF KW - CCL20 KW - CCR6 KW - Dendriplex KW - hMSC KW - rTBI ER -