Nose-to-brain delivery of human muse cells enhances structural and functional recovery in the murine ischemic stroke model

Muse cells are endogenous, non-tumorigenic, pluripotent-like stem cells already applied to clinical trials based on intravenous injection. They can selectively home to the post-infarct area, replenish apoptotic neural cells by phagocytosis-induced differentiation, and enhance functional recovery. The effect of nose-to-brain delivery of Muse cells on cerebral infarct was examined. Permanent middle cerebral artery occlusion model BALB/c mice received intranasal administration of either human Muse cells (6.0 × 10⁴ cells), high-dose human-mesenchymal stem cells (MSCs) (1.6 × 10⁶ cells), low-dose human-MSCs (6.0 × 10⁴ cells), or vehicle at 7 days after onset. An accelerated rotarod test and a histological assessment were done. The vehicle- or low-dose MSC groups showed no significant improvement in the rotarod test. In the high-dose MSC group, motor function was transiently recovered, but the therapeutic effect disappeared thereafter. The Muse group continuously improved motor function, with statistical significance to the other groups. The engraftment of administered cells in the peri-infarct area was the highest in the Muse group, while few cells were detected in other groups. 63.6 ± 8.5% and 26.2 ± 3.0% of Muse cells were positive for NeuN and GSTpi, respectively. Intranasal administration of Muse cells might be a viable approach to improving functional recovery with less invasiveness after ischemic stroke.