Improved efficacy of cell-based therapy in a cerebral infarction model by cotreatment with hyaluronan

Background Cerebral infarction (ischemic stroke) is a leading cause of morbidity and mortality worldwide. Cell-based therapy has shown some benefits during the acute phase post-stroke, but longer-term efficacy is limited by insufficient expression of cytoprotective, growth-promoting, angiogenic, and immunomodulatory factors. We speculated that cotreatment with hyaluronan would enhance the therapeutic efficacy of bone marrow mononuclear cell (MNC) injection in a mouse stroke model. Methods Mice subjected to middle cerebral artery occlusion (MCAo) were injected with MNCs, hyaluronan, or the combination (HA + MNCs), and subsequently tested for sensorimotor recovery using the neurological severity score (mNSS) test battery, von Frey tactile sensitivity test, and wire-hanging test 3, 5, and 7 days post-MCAo. Results Combined treatment with MNCs plus hyaluronan enhanced focal hyperemia in the acute stage post-MCAo compared to either treatment alone. In addition, combined treatment augmented local angiogenesis, promoted neuronal survival in the ischemic field, reduced infarct size, and improved sensorimotor recovery in the weeks post-MCAo. These beneficial effects were associated with reductions in reactive gliosis and T-cell activation as well as enhanced secretion of anti-inflammatory cytokines. In conclusion, hyaluronan cotreatment may enhance the therapeutic efficacy of cell-based therapy following cerebral infarction.