Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke

Ischemic stroke causes vascular and neuronal tissue deficiencies that could lead to substantial functional impairment and/or death. Although progenitor-based vasculogenic cell therapies have shown promise as a potential rescue strategy following ischemic stroke, current approaches face major hurdles. Here, we used fibroblasts nano-transfected with Etv2, Foxc2, and Fli1 (EFF) to drive reprogramming-based vasculogenesis, intracranially, as a potential therapy for ischemic stroke. Perfusion analyses suggest that intracranial delivery of EFF-nanotransfected fibroblasts led to a dose-dependent increase in perfusion 14 days after injection. MRI and behavioral tests revealed similar to 70% infarct resolution and up to similar to 90% motor recovery for mice treated with EFF-nanotransfected fibroblasts. Immunohistological analysis confirmed increases in vascularity and neuronal cellularity, as well as reduced glial scar formation in response to treatment with EFF-nanotransfected fibroblasts. Together, our results suggest that vasculogenic cell therapies based on nanotransfection-driven (i.e., nonviral) cellular reprogramming represent a promising strategy for the treatment of ischemic stroke.

Automated summary

Intracranial delivery of EFF-nanotransfected fibroblasts resulted in a dose-dependent increase in perfusion 14 days post injection. Mice treated with EFF-nanotransfected fibroblasts showed around 70% infarct resolution and up to 90% motor recovery. Immunohistological analysis confirmed increased vascularity, neuronal cellularity, and reduced glial scar formation in response to treatment with EFF-nanotransfected fibroblasts, suggesting a promising strategy for ischemic stroke treatment.